May 21, 2025 • 47 mins
Unlock the complexities of menopausal hormone therapy for breast cancer survivors in this episode of the Speaking of Women's Health podcast. Join Host Dr. Holly Thacker and her esteemed guest, Dr. Holly Pederson, as they navigate the intricate world of genetic testing and its crucial role in guiding treatment decisions.
Dr. Pederson, a leading expert in the field, emphasizes the importance of revisiting genetic tests conducted before 2013 to ensure breast cancer survivors receive the most informed care. They explore the advancements in genetic science and discuss the layers of genetic risk, revealing how these insights can revolutionize both treatment and screening practices.
Their conversation further examines the challenges faced by elderly women considering hormone replacement therapy. This episode offers a thoughtful reflection on the unique considerations for breast cancer survivors, especially those with BRCA mutations, and the importance of individualizing patient care.
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Episode Transcript
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Speaker 1 (00:06):
Welcome to the Speaking of Women's Health
podcast.
I'm your host, dr Holly Thacker, the Executive Director of
Speaking of Women's Health, andI am back in the Sunflower House
for a new episode in Season 3with a guest we've had before,
dr Holly Peterson, and we aregoing to talk about prescribing
(00:31):
menopausal hormone therapy forbreast cancer survivors.
And we've had a lot ofdiscussion about genetics in the
past breast cancer, genetics,hormone therapy, breast cancer
survivors but we're going tospecifically talk about the use
of hormone therapy Now.
Dr Peterson is a professor ofmedicine at the Cleveland Clinic
(00:55):
Lerner College of Medicine herein Cleveland, ohio, and she is
a board-certified internist andthe former director of the
medical breast program at theCleveland Clinic, where she
actually essentially foundedthis program, and she serves as
a professor of medicine andshe's actively involved in very
(01:18):
interesting clinical researchand has a co-appointment in the
Lerner Research Institute andhas a co-appointment in the
Lerner Research Institute.
Dr Peterson graduated Phi BetaKappa from the University of
California, santa Barbara, inbiochemistry and molecular
biology, and then she completedboth an internship and a
(01:39):
residency at the University ofCalifornia, san Francisco, where
she earned the distinction ofAlpha Omega.
Alpha Additional educationincludes clinical genetics
fellowship at the ClevelandClinic in 2008 and the City of
(02:00):
Hope course in cancer geneticrisk assessment in 2017.
She has served on theprestigious National
Comprehensive Cancer Network,risk Reduction and Genetic
Committees and she speaksnationally and internationally
(02:20):
with a specific focus on themanagement of women and
high-risk patients for breastcancer genetics, and she's also
developed an internal fellowshipfor training medical breast
clinicians, a program which shehelped create.
Welcome, dr Peterson, it'sgreat to have you on the podcast
(02:40):
again, thank you so much forhaving me back.
Speaker 2 (02:43):
I really appreciate it on the podcast.
Speaker 1 (02:46):
again, thank you so much for having me back.
I really appreciate it.
Speaker 2 (02:49):
So we have so many similarities.
You know I wanted to mentionsomething.
I just wanted to mentionsomething.
I listened to your Highlightsof the Year podcast and it was
just fabulous recently about allof your podcasts.
I think it's just great thatyou're doing this and raising
awareness about so manydifferent issues.
Just because I have to saysomething about genetics.
(03:12):
You know the guidelines arebecoming complicated and really
most women who develop breastcancer should look into genetic
testing.
That's sort of you know.
Unless you're over 65 andqualify for genetic testing
based on previous guidelines,all women should really
(03:33):
investigate it, and so I wantedto kind of make that a little
bit more clear for women.
And if you were tested beforethe fall of 2013, the testing
has improved drastically, socome on back.
Just had to throw that in, I'msorry.
Speaker 1 (03:52):
Yes, no, no.
That is very important andwe've made that point, and I
always like to go back and lookwhen I'm seeing patients in the
clinic, because a lot of peoplecan't exactly remember when they
had the testing, and I thinkit's important.
Even though it's uploadedelectronically, people should
really keep their hard copies, Ithink, because they may move
(04:16):
and change and we're expecting,of course, continued advances in
this very important field.
I was just going to say, goingover your bio, we have so many
similarities, not just our firstname and our similar age, and
that we have three adult,wonderful children both.
AOA and both founding a reallykind of innovative
(04:37):
interdisciplinary women's healthkind of having the vision to
see that different fields needto come together for the benefit
of the female patient.
And so kudos to you and all ofyour expertise, and hopefully
we'll have some time to talkabout your recent award and some
of your recent research.
(04:58):
And I know that this podcast isprimarily for any woman or any
person anywhere who wants tolisten, and it's free.
You can hit, subscribe orfollow anywhere you follow
podcasts, but we do have a lotof physicians and nurses and
clinicians who do tune in, sosometimes we go to some higher
level things, but I think it's abenefit for everyone.
(05:19):
So I wanted to saycongratulations.
I understand that you haveretired from clinical practice,
but not academic practice.
Is that right?
Speaker 2 (05:32):
Yes, I'm still doing research and education, thank
you.
Speaker 1 (05:38):
And that is so important.
But certainly if there's anylisteners that want to come to
the medical breast program, wehave several people available,
including a lot of protégés andpeople that have trained under
Dr Peterson, so I think that isso important.
So, before we talk about ourmajor that's a great program.
Speaker 2 (05:59):
You know, I was just going to say the medical breast
program.
You know it providesdiagnostics, personalized team
and the team is wonderful andthey continue on with clinical
(06:26):
practice.
But I'm currently myself notpracticing.
Speaker 1 (06:32):
And I wondered if you wanted to talk a little bit
about Karis Eng.
Dr Karis Eng, an MD PhD.
She was certainly my sonStetson Thacker.
Dr Stetson Thacker, who's beenon our podcast, who's a PhD in
molecular medicines mentor, andI know she was a mentor to you
and so many people and shepassed last year.
Speaker 2 (06:56):
It was a rough year.
We lost both Dr Joseph Crow,who founded the Breast Center,
in February another medicalgiant and Dr Karis Eng in
October.
Both too soon and very, verysad losses.
But you know, for personallyand professionally they were
(07:17):
outstanding mentors and teachers, and scientists and physicians
and scientists and physicians.
Speaker 1 (07:32):
Yes, dr Crow I stood by him and Dr Alice Rim, in
charge of our breast imaging, in2002 when we opened our Center
for Specialized Women's Healthand really expanded upon not
just having breast services buthaving other specialty services.
And Dr Eng has won so manynational awards and made so many
original discoveries, so it'sreally quite a legacy, and we
certainly have, don't?
(07:52):
We have the world's leadingexperience in nipple sparing,
mastectomy and reconstruction.
Speaker 2 (08:00):
We do you know, our genetic and genomic program is
really unparalleled and theBreast Center, with its
multidisciplinary approach, hasreally been on the cutting edge
in many fields and certainly inthe field of nipple-sparing
mastectomy.
We probably have the largestsingle institution experience in
(08:23):
the world, you know,demonstrating the safety of
nipple sparing mastectomy evenin very high risk patients.
Speaker 1 (08:32):
And such wonderful outcomes.
And I even have some patientswho volunteer to come in and see
other patients who are thinkingabout this, to actually in the
exam room give them a littlelook about how wonderful the
cosmesis is.
So I think that for women whohave to deal with breast cancer,
(08:53):
so many of them can livecompletely full lives, not miss
a beat.
The therapies are so much moretargeted, outcomes are improving
and many women who are youngwomen go on and have children,
and women who don't want to havefurther children or are past
that stage in life or interestcan move into midlife and beyond
(09:17):
and expect to have the sametype of life as other women.
And so, since in the last 15plus years we've had increasing
research that shows thatmenopausal hormone therapy is
really the thing that we offerto midlife women that extends
life and reduces disease burden,and I've always been a
(09:39):
proponent of just because youmight have been unlucky enough
to have severe problems maybeneeding an organ transplant,
maybe having cancer, maybehaving had a heart attack or
serious blood clots, yeah, orvascular problems that those
(10:01):
women shouldn't be furtherdenied other common therapies.
So that gets us into usingmenopausal hormone therapy in
breast cancer survivors,something I've done for
essentially my whole career, butI think it's catching on a
little bit more, and I wantedyou to talk about it from your
(10:24):
breast perspective.
Speaker 2 (10:27):
You know I mean breast cancer is the most common
cancer in the United States andworldwide, aside from skin
cancer, and the good news is isthat treatments are improving
and mortality is improving inall different types of breast
cancer.
And it's important to rememberthat breast cancer is not just
(10:50):
one disease.
It's a group of entirelydifferent diseases that have
entirely different rates ofrecurrence and patterns of
recurrence and methods oftreatment and methods of
surveillance.
But what we do know we know acouple of things and you bring
(11:13):
to light very important pointsis that we have more and more
survivors and we have more andmore young survivors.
And we also know that mostwomen who have breast cancer
don't die from breast cancer.
They actually are more likelyto die from cardiovascular
(11:33):
disease or stroke.
And in women who are long-termsurvivors of breast cancer, we
have had a dogmatic approach inour multidisciplinary community
to absolutely not considersystemic menopausal hormone
(11:56):
therapy in a woman who's had ahistory of breast cancer due to
concern, and it's largely basedon theoretical concerns and not
actual medical data.
But we don't want to do any harmcommunity in terms of hormone
(12:23):
replacement following a breastcancer diagnosis.
But this question is far fromanswered and I think that you
know.
It's just fascinating thatyou've been taking women
individually, looking at theirpersonal risk for developing a
new cancer, their likelihood ofbeing at risk for developing
(12:49):
another cancer, looking at thetype of cancer that they had,
how they were treated, whetherthey responded well to treatment
and how far out they are fromtheir cancer.
And you've made the decision,the judgment call, in those
situations, with a womanunderstanding all of those
(13:10):
factors, she may choose, whenshe exhausts non-hormonal
methods of, you know,controlling menopausal symptoms,
to consider hormonal menopausalhormone therapy, to consider
hormonal menopausal hormonetherapy, and it really has.
You've been a trailblazer inthis field.
In fact, there was a recentstudy published by Dr Cheryl
(13:32):
Kingsberg at UH, who dida surveyof oncologists and oncology
patients and actually found youknow, in the real world about
15% of breast cancer survivorsin that cohort were currently
taking systemic menopausalhormone therapy.
(13:56):
So you're not alone, andhopefully you will be less alone
as time goes on if we're ableto answer these types of
questions.
Speaker 1 (14:07):
It's so interesting because I think that it's
twofold why there's been thishesitancy.
Well, it's probably threefold.
One, I think women tend to bemore anxious, and so if the
patient's projecting anxiety andthe physician or the clinical
team wants to do no harm, theypull back.
(14:28):
So part of it is the woman.
I think a second part of it hasto do with subtle ageism, in
that we accept risk for youngerwomen, for instance with
hormonal contraceptives whichhave a higher rate of blood clot
, and then we accept like hardlyany risk or zero risk with
(14:49):
menopausal hormones, andeverything has a risk Driving to
your doctor's office has a risk.
So this misunderstanding ofrisk, absolute and relative risk
is another factor, and the factthat we allow younger women who
have more life to live, toundergo therapies if they want
(15:14):
to control their reproductivelife, prevention of pregnancy.
But then at menopause, ifyou've lived long enough to lose
your hormones, we say oh, toobad, too bad, suffer.
And so I think that's a bigproblem.
And young women who've hadbreast cancer after their
treatment they can go on and getpregnant if they want to.
(15:35):
And that's way higher levels,much higher levels than what we
would ever do for menopause.
And so I think, having more ofthis perspective and also
understanding that the averageman who's older than a woman,
who's post-menopausal, has moreestrogen than she has.
(15:56):
How is that fair?
That's how I got involved inthis field, Because I just
thought it was so unfair.
And you're listening to theSpeaking of Women's Health
podcast.
I'm your host, Dr Holly Thacker, the Executive Director of
Speaking of Women's Health.
I'm at the Center forSpecialized Women's Health and I
run our Specialized Women'sHealth Fellowship.
And I am speaking to specialguest.
(16:17):
Dr Holly Peterson, who foundedour Medical Breast Program, is a
medical breast high-risk breastcancer expert and has done some
cutting-edge research.
And we're talking about safety,risk benefits, alternatives,
exceptions to menopausalhormones.
I want to talk a little bitmore, first about risk
(16:38):
assessment and your recentresearch.
Tell me about that combinedrisk score and what your
research found and how it's oneof the top 10 advances in
genomic medicine.
Speaker 2 (16:52):
Well, you are so funny.
I just love the way your brainworks.
I mean, you've brought up atleast 15 topics in that little
blurb there.
But you know, when you'retalking about risk, you need to
assess your own risk and we'lltalk about that but you need to
also, whenever you attend amedical visit, look at the risks
(17:18):
of doing something and look atthe risks of not doing something
, because that's actuallyrelevant here.
You mentioned that estrogen isthe most effective therapy for
menopausal symptoms.
We do know that women whoundergo early surgical menopause
(17:40):
or early iatrogenic menopauseMaybe what that means is we
cause the menopause, maybe byeither surgery or chemotherapy,
but those women we know are atrisk for early cardiovascular
disease and acceleratedosteoporosis, amongst other
(18:03):
things.
And so young women who undergoiatrogenic menopause at an early
age are certainly at higherrisk of those issues.
And so, while we need to worryabout estrogen per se but that's
(18:23):
debatable and we'll talk aboutthat we also need to be
cognizant that these young womenshould have estrogen in their
bodies and we may becontributing to cardiovascular
disease and osteoporosis bywithholding it in some
situations.
Now, in terms of riskassessment young women really
(18:50):
just a risk assessment is justto look at their family history
very carefully and look for redflags.
That might be a sign of, youknow, of hereditary syndromes,
but also just of being at higherrisk for breast cancer.
The things that we can all doare achieve and maintain our
ideal body weight and limitalcohol consumption.
(19:12):
But if there's a family historyof early breast cancer, say,
you know, under the age of 50,or ovarian or pancreatic cancer
at any age metastatic prostatecancer, multiple primary breast
cancers, male breast cancer, asyou brought up, Ashkenazi,
Jewish ancestry as there may bea one in 40 chance of carrying a
(19:36):
BRCA mutation, women need to beinherently aware that they may
be at much higher risk thananother woman.
Now that doesn't necessarilymean that they would not be
eligible for hormone therapy,for hormone therapy, either
(20:01):
contraceptive or menopausal, buta woman should know that she is
at a baseline higher risk.
When you talk about thecombined risk score or a way to
further substratify your riskthe youngest women we really
just ask about family history.
Then, when women get a littlebit older, say in their 30s, we
(20:22):
can use mathematical models likethe Tyra Kuzik model out of the
United Kingdom to furtherestimate their risk using
traditional risk factors.
But what we've added to that isadding your own genetics into
the mix, you know, becausethat's just a mathematical
(20:43):
calculation, and what we'velearned is that there are
essentially three layers ofgenetic testing, if you will.
There's the highly penetrantgenes like BRCA1 and BRCA2 and
PALB2.
There's also in that group thatare more rare CDH1, STK11, TP53
(21:07):
, and P10.
Those are all just alphabetsoup, but those are the real bad
genes and the most important ofthose are BRCA1, BRCA2, and
PALB2.
There's another level ofgenetic abnormality seen in
moderate risk genes such asCHECK2 or ATM, and the risk
(21:30):
that's conferred by those genesis similar to that of like.
If you have a benign biopsyshowing atypical hyperplasia,
it's not as much of a red flagas you might see with someone
who has triple negative breastcancer at age 35.
(21:51):
That might be a sign of BRCA1.
But many people carry these ATMand CHECK2 mutations.
They're not uncommon and theymay be causal.
But what we've discovered isthat there's a third level of
genetics that's kind of likenoise at the bottom.
There's over 300 singlenucleotide polymorphisms that
(22:13):
have been linked to breastcancer, that are independently
inherited from each parent, andso your complement of those 300
SNPs might be totally differentfrom a sibling of yours, and
that polygenic risk score, whichis a weighted aggregate of the
(22:37):
effects of those SNPs, whichneeds to be calibrated by
ancestry, gets prettycomplicated.
That polygenic risk score, incombination with the
mathematical risk model, canreally help to further
substratify women and what wefound is that in looking at
(22:59):
young Black women and youngHispanic women who develop
breast cancer, lo and behold, 50to 60% of those women had no
family history of breast orovarian cancer in a first or
second degree relative, buttheir polygenic risk score was
(23:20):
very different from even womenwho qualified for genetic
testing and were also black orHispanic but had negative
genetic testing and didn't getcancer.
So the ones who got breastcancer were very different in
terms of the polygenic riskscore from the ones who didn't
(23:41):
get cancer and this may changeour whole screening paradigm.
Ultimately, you know, we maystart looking at younger women
and offering them not onlygenetic testing for the highly
penetrant and moderatelypenetrant genes, but perhaps
even in the future, offeringthis test to see what women
(24:07):
might require more closesurveillance, say with breast
MRI.
So that's really what myresearch pertains to, not so
much with the question at handwith hormone in the breast
cancer survivor, but it isimportant for that survivor to
risk stratify.
(24:28):
I think that that's one of thefirst things a practitioner has
to think about when she'slooking at a breast cancer
patient who's contemplatinghormone therapy is what is her
level of risk?
And you can't use the riskmodels with breast cancer
patients because they're notdesigned for that.
(24:50):
However, the polygenic riskscore has been used
experimentally in severalstudies and predicts the
likelihood of developing a newcancer on the other side.
That's been shown in threeseparate studies, and so the
(25:10):
polygenic risk score cansubstratify risk in the general
population within a gene.
Say, if you had checked to, youcan check your polygenic risk
score to see whether you'rehigher or lower risk within that
genetic group.
It can be used to potentiallyidentify low risk women in the
(25:34):
long run, to potentiallyidentify low-risk women in the
long run, we're hoping.
But it also can help newlydiagnosed patients, not
currently in the clinicalsetting but in the research
setting, to identify their riskfor contralateral disease.
So it's very excitingtechnology.
You're going to see it in alldisease states.
It's not just breast cancer,it's not just cancer.
(25:55):
You're going to see it in heartdisease, diabetes.
These polygenic risk scores aregoing to help you to stratify
your risk in a lot of differentareas.
Speaker 1 (26:07):
That is so interesting.
Do you have any predictionsabout when you think that this
will be more standard practiceand recommended by the NCCN?
Speaker 2 (26:20):
So the validation studies date back to 2015.
We really have had solidvalidation studies for a very
long time, but the NationalComprehensive Cancer Network, or
NCCN, has concerns about whichPRS to use.
(26:43):
Some of them are not validatedin different ancestries because
these tests were originallydeveloped and validated in
Caucasian women of Europeandescent and the risk of these
different SNP alleles, thedifferent SNP DNA pieces, the
(27:07):
risk is different in differentancestries and so you have to
account for that and not all ofthe tests do.
The other issue is that manypractitioners don't really
understand how they would usethis going forward, and until
there are clear guidelines tohelp practitioners, help
(27:31):
patients, make those decisions,we're not going to see it in
clinical care.
You know, maybe in about, if Iwere to guess, three years or so
.
Three years or so althoughclinically they are available
but they're not recommended bygoverning bodies at this time.
Speaker 1 (27:54):
I have to say in my own experience, because years
ago, I mean before, weunderstood the benefits of
longevity with menopausalhormone therapy and post-Women's
Health Initiative, when therewas all this media on a
scientific study but kind ofnon-scientifically communicated
to the public, that caused a lotof anxiety where a lot of women
(28:17):
threw away their hormonetherapy.
I would regularly do the Galemodel or sometimes the Tyler
Cusick model and calculate howlong they had been on hormones.
We even offered for a point intime breast ductal lavage to see
if we saw atypical breast cells.
To try to encourage women forchemo prevention, because there
are agents that are approved.
To try to encourage women forchemo prevention because there
are agents that are approved totake to reduce your risk of
(28:40):
being diagnosed with breastcancer without any evidence
showing that it reduces deathrates.
But I found that kind of anunsatisfying type of practice
because some of the highest riskwomen I identified were not
interested in any kind ofpreventive treatment.
And so I think on a populationlevel yeah, for education.
(29:04):
Like people, women I think, areusually pretty invested in
having a pap smear to screen forearly cervical cancer and I
think more and more we're tryingto get to that 80% threshold in
adults over 45 to screen forcolon cancer, colorectal cancer.
I think most women are prettyaccepting of the mammogram and
(29:25):
breast imaging, which I know wehave differences of opinion in
imaging, just because I do seethe problem of over diagnosis
because then women don't wanthormone therapy or they stop
their hormone therapy.
Like I've got a patient comingin who's past the age that we
even do screening by theAmerican Cancer Society, but she
(29:47):
had to have her mammogrambecause she's so healthy,
because she's been on hormonesfor 35 years and of course
there's an abnormality, ofcourse there's a biopsy, it's
not cancer but you know she's atincreased risk, which of course
a woman of advanced age justage alone is at an increased
risk.
So when there's not really goodunderstanding, I don't think
(30:10):
amongst not just patients butpeople in the medical field
about what that risk actuallytranslates to.
It causes so much anxiety.
One thing that I do is,especially when I see a younger
woman who's diagnosed withbreast cancer, is there are
younger women who are notprevented from having their own
(30:31):
ovarian hormones, based on thetype of cancer or it being
estrogen negative.
Or maybe they've undergonetherapy that stopped their
period for a while but then theyresumed ovarian function and
they continue to have their ownhormones until the age of
menopause.
And then they go into menopauseand then they think they can't
have hormones, even though theyjust had it for the last 10
(30:54):
years.
Or I see women who may be inmenopause but they saved some
embryos and they got pregnantbecause they wanted to be a mom.
They had really high estrogenlevels for nine months and felt
terrific and then postpartum iftheir ovaries didn't start
working again, which many timesis the case.
(31:14):
All of a sudden, horrible hotflashes and the women don't even
want to accept local vaginalestrogen, which we offer to
women, even undergoing activebreast cancer treatments if
needed.
So I wondered if you had anyperspective on that.
Speaker 2 (31:30):
On those next 10 questions.
All right, I'm going to startwith the sensitivity of
screening mammography in elderlywomen.
There have been no studies ofmammography in women over the
age of 75.
And major radiologicassociations like the American
College of Radiology, becausethe sensitivity is so good when
(31:52):
the density goes down, most ofthe you know of the prominent
experts in that field feel thatprobably it's okay to continue
mammography till 90.
Speaker 1 (32:06):
I know you're going to kill me, but don't, don't
don't start now I want to, Iwant to address some of your
other questions, so you know,and I think that's fine if women
do that, but I just don't wantthem coming crying to me when
they're told that they can't beon hormones anymore.
(32:28):
And they have zero symptoms andwe can't tell them that it's,
that it's not a false positive.
Speaker 2 (32:35):
Yeah.
Speaker 1 (32:35):
Yeah.
Speaker 2 (32:36):
Yeah, you know, and there are fewer false positives
in the older women but anywayslet's return to our topic, which
you know you.
You know so much about thehistory of the women's health
initiative study and whathappened with that, and I'm
going to try to summarize it ina brief way.
(32:56):
But you know, when did youstart at the clinic, holly I?
Speaker 1 (33:03):
joined the staff in 1990.
, 1990.
Speaker 2 (33:08):
Okay, I came in 1997.
And so we were both really in onthe beginning of all of this.
You know, in the early 90s Ithink it was 1992 when the
Women's Health Initiative studystarted you know, the largest
study in women ever performed,$700 million or so where really
(33:29):
the question was to answerwhether menopausal hormone
therapy reduced the risk ofcardiovascular disease.
And so, rather than choosing theappropriate age of women to
really answer hormonal questionsthey included the majority of
women were over the age of 60,smokers, overweight.
(33:53):
They were really looking at adifferent question, and in 2002,
the study was suddenly stoppedbecause there were big media
releases that there was a 26%increase in breast cancer risk
(34:13):
with hormone replacement therapy, as it used to be called, and
what they didn't talk about, asyou mentioned initially, was the
increase in absolute risk thatthat may confer to a woman.
Risk at the age of 50 is 1.3%or 1.5% over the next five years
(34:42):
.
If she increases her risk overthe next five years by 26%, she
goes from a whopping 1.5% to a1.7% or 8%, which most women
will accept in terms of absoluteincrease in risk.
If this had been explained in2002, I don't think that we
(35:07):
would be sitting and having thisdiscussion in 2024.
And, in fact, what they show-2025,.
Speaker 1 (35:15):
We're in 2025.
Speaker 2 (35:17):
2025,.
Oh no, you're going to send mychecks back.
No, so it's fascinating becausein 1994, a paper was published
saying estrogen replacementtherapy in breast cancer
survivors.
It's time to look at this.
(35:38):
This was in 1994.
And many trials started lookingat this question would it be
okay to consider hormonereplacement in breast cancer
survivors?
And unfortunately, most ofthose trials were stopped.
When the Women's HealthInitiative trial was stopped
(36:00):
because everyone was nervousabout continuing several
prospective studies which failedto accrue the appropriate
number of patients and reallydidn't answer the questions that
(36:21):
they set out to answer, andwe're now making clinical
decisions without the data thatwe need.
I think that the most importantpart of this question is that
we need further study in thisarea, but what we do know is not
(36:44):
as ominous as most people think, and I wanted to kind of go
over that with you.
So you know, one thing is thatwe allow women who have invasive
breast cancer, that's estrogensensitive, to stop their
(37:04):
hormonal therapy, theirendocrine therapy, their
tamoxifen or aromatase inhibitortherapy, in order to have a
baby and breastfeed.
And that's a very high hormonalstate to have a baby and
breastfeed and that's a veryhigh hormonal state.
You were mentioning that.
We allow them, you know thatopportunity, or encourage it,
following their treatment.
(37:25):
We actually allow it in themidst of their treatment.
Speaker 1 (37:29):
And those women have been shown, yeah, to do.
Speaker 2 (37:32):
Well, you know.
And the other group that youknow is reassuring is the
patients with the highlypenetrant gene mutations,
patients with BRCA1 and BRCA2,who are at very high risk when
we recommend that they havetheir tubes and ovaries removed
because there's no goodscreening for ovarian cancer.
(37:55):
We have been giving routinelymenopausal hormone therapy back
to those women and have notshown an increased risk of
breast cancer.
Those are the highest riskwomen that you're going to find.
Women who do not have a geneticmutation, who have survived
(38:16):
breast cancer, have about a 0.4%per year chance of having
another breast cancer develop,and so it's very, very low and
most people don't realize that.
But if they do have a geneticmutation, of course their
(38:37):
likelihood, if they retain theirbreast tissue, is higher.
But you know the treatments arebetter.
Women are more likely to becured of this disease.
You know we do give estrogen.
You know we allow high estrogenstates like pregnancy, even in
the midst of cancer treatment,and the BRCA population
(39:02):
tolerates menopausal hormonetherapy very well following
their risk-reducing surgery, andwe give it to the time of
natural menopause in women whohaven't had breast cancer.
Perhaps we should be givingthat longer, and that's another
question that I have in terms ofthese women, but you brought up
(39:22):
what about the woman with ERnegative disease or breast
cancer that does not express theestrogen receptor?
Would it be okay, in thosewomen who have invasive breast
cancer that's estrogen negative,to consider hormone replacement
(39:43):
therapy earlier?
My argument is no.
I want to go over the differenttypes of breast cancer and
their typical recurrencepatterns and rates.
Dcis or ductal carcinoma insitu, which is stage zero breast
(40:09):
cancer, it's just stage zerothe potential to well, I believe
it's breast cancer, but that'sa different.
That's a different if you don'tundergo radiation.
(40:33):
There's about a 30% localrecurrence rate and 15% and 50%
of those are invasive.
So it's hard for me to notclassify it in the cancer you
know category when you haveinvasive recurrences occurring
50% of the time.
But anyways, distantrecurrences are very rare less
than 2%.
So a woman who is several yearsout from a DCIS diagnosis, you
(40:56):
know is very different from awoman who has has stage two ER
positive disease, you know, whois in the midst of therapy and
there's everything in between.
So there's triple negativebreast cancer and HER2 positive
breast cancer which usuallyoccur, recur, if they're going
(41:19):
to recur in the first five yearsand typically in the first
three years.
And so a woman who's five yearsout from ER negative breast
cancer or HER2 positive breastcancer, you know, is in a good
place.
We don't have data thathormone's okay, but we know that
(41:42):
she's in a good place in termsof her breast cancer diagnosis.
With estrogen sensitive, her2negative breast cancer the tail
for recurrence goes out muchfurther and those women need to
understand that they might havea recurrence completely
(42:04):
unrelated to hormone replacementor no hormone replacement
because of their originaldisease.
But let me tell you somethingabout ER negative disease that
bothers me in terms of saying,oh, it must be okay because it
doesn't contain estrogenreceptors.
Women with BRCA1 mutations whohave triple negative breast
(42:31):
cancer and have their ovariesremoved in the first year have a
markedly improved survival rateas compared to women with
triple negative breast cancerand BRCA1 who have their ovaries
removed much later, and thatmakes me worry a little bit.
(42:55):
There's something, and it maynot be the estrogen, but there's
something about the absence ofthe ovary that is promoting
better breast cancer survival,and so there's something about
that that gives me pause aboutestrogen replacement right away.
(43:17):
Now, you know, five years in it,you know, with a triple
negative breast cancer it's acompletely different discussion.
But I don't think that one canjust assume that if it's
estrogen receptor negative, it'sokay, because there are.
There are just different thingsthat we've found.
(43:38):
For instance, there's anAmerindian snip that's found in
the Hispanic population that isprotective from breast cancer.
What it does is it lowersestrogen levels and lowers
(43:59):
breast density, but it preventstriple negative disease, you
know.
And so there's a lot about thatthat we don't understand, and
so I do have a little hesitationwhere many people don't because
of those issues.
(44:19):
You know, a patient with DCISor who's five years out from
triple negative disease or HER2positive disease, or a person
who's ER positive, HER2 negative, who's doing very well and has
a very low likelihood ofrecurrence and is five years out
, you know, those are thepatients I believe that we
(44:40):
should start with and be talkingto and be enrolling in clinical
trials.
Speaker 1 (44:48):
So this has just been such an excellent discussion
and we'll have to bring you backon Dr Peterson and maybe even
have you guest host for me,because you call yourself the
other Dr Holly, so that would bewonderful.
Speaker 2 (45:04):
Oh, I'd love to do that.
Speaker 1 (45:06):
It's great to get other perspectives of really
experienced clinician scientists, scholars and leaders
scientists, scholars and leaders.
I would mention to ourlisteners who are physicians and
clinicians that we have asection on
speakingofwomenshealthcom undertools for physicians, including
links to CME, including links tomenopausalearningorg, where we
(45:32):
have some lectures that youcould view of a breast
oncologist talking about the useof hormone therapy in breast
cancer survivors, as well asheart disease and many other
topics.
So thank you to our listenersand to Dr Peterson for joining
us on the Speaking of Women'sHealth podcast.
(45:53):
Please subscribe on ApplePodcasts, spotify or tune in or
wherever you listen.
Share the podcast, give us afive-star rating and I hope
you'll tune in for futureepisodes.
Remember be strong, be healthyand be in charge.
Thank you.
Welcome to the Speaking of Women's Health
podcast.
I'm your host, dr Holly Thacker, the Executive Director of
Speaking of Women's Health, andI am back in the Sunflower House
for a new episode in Season 3with a guest we've had before,
dr Holly Peterson, and we aregoing to talk about prescribing
(00:31):
menopausal hormone therapy forbreast cancer survivors.
And we've had a lot ofdiscussion about genetics in the
past breast cancer, genetics,hormone therapy, breast cancer
survivors but we're going tospecifically talk about the use
of hormone therapy Now.
Dr Peterson is a professor ofmedicine at the Cleveland Clinic
(00:55):
Lerner College of Medicine herein Cleveland, ohio, and she is
a board-certified internist andthe former director of the
medical breast program at theCleveland Clinic, where she
actually essentially foundedthis program, and she serves as
a professor of medicine andshe's actively involved in very
(01:18):
interesting clinical researchand has a co-appointment in the
Lerner Research Institute andhas a co-appointment in the
Lerner Research Institute.
Dr Peterson graduated Phi BetaKappa from the University of
California, santa Barbara, inbiochemistry and molecular
biology, and then she completedboth an internship and a
(01:39):
residency at the University ofCalifornia, san Francisco, where
she earned the distinction ofAlpha Omega.
Alpha Additional educationincludes clinical genetics
fellowship at the ClevelandClinic in 2008 and the City of
(02:00):
Hope course in cancer geneticrisk assessment in 2017.
She has served on theprestigious National
Comprehensive Cancer Network,risk Reduction and Genetic
Committees and she speaksnationally and internationally
(02:20):
with a specific focus on themanagement of women and
high-risk patients for breastcancer genetics, and she's also
developed an internal fellowshipfor training medical breast
clinicians, a program which shehelped create.
Welcome, dr Peterson, it'sgreat to have you on the podcast
(02:40):
again, thank you so much forhaving me back.
Speaker 2 (02:43):
I really appreciate it on the podcast.
Speaker 1 (02:46):
again, thank you so much for having me back.
I really appreciate it.
Speaker 2 (02:49):
So we have so many similarities.
You know I wanted to mentionsomething.
I just wanted to mentionsomething.
I listened to your Highlightsof the Year podcast and it was
just fabulous recently about allof your podcasts.
I think it's just great thatyou're doing this and raising
awareness about so manydifferent issues.
Just because I have to saysomething about genetics.
(03:12):
You know the guidelines arebecoming complicated and really
most women who develop breastcancer should look into genetic
testing.
That's sort of you know.
Unless you're over 65 andqualify for genetic testing
based on previous guidelines,all women should really
(03:33):
investigate it, and so I wantedto kind of make that a little
bit more clear for women.
And if you were tested beforethe fall of 2013, the testing
has improved drastically, socome on back.
Just had to throw that in, I'msorry.
Speaker 1 (03:52):
Yes, no, no.
That is very important andwe've made that point, and I
always like to go back and lookwhen I'm seeing patients in the
clinic, because a lot of peoplecan't exactly remember when they
had the testing, and I thinkit's important.
Even though it's uploadedelectronically, people should
really keep their hard copies, Ithink, because they may move
(04:16):
and change and we're expecting,of course, continued advances in
this very important field.
I was just going to say, goingover your bio, we have so many
similarities, not just our firstname and our similar age, and
that we have three adult,wonderful children both.
AOA and both founding a reallykind of innovative
(04:37):
interdisciplinary women's healthkind of having the vision to
see that different fields needto come together for the benefit
of the female patient.
And so kudos to you and all ofyour expertise, and hopefully
we'll have some time to talkabout your recent award and some
of your recent research.
(04:58):
And I know that this podcast isprimarily for any woman or any
person anywhere who wants tolisten, and it's free.
You can hit, subscribe orfollow anywhere you follow
podcasts, but we do have a lotof physicians and nurses and
clinicians who do tune in, sosometimes we go to some higher
level things, but I think it's abenefit for everyone.
(05:19):
So I wanted to saycongratulations.
I understand that you haveretired from clinical practice,
but not academic practice.
Is that right?
Speaker 2 (05:32):
Yes, I'm still doing research and education, thank
you.
Speaker 1 (05:38):
And that is so important.
But certainly if there's anylisteners that want to come to
the medical breast program, wehave several people available,
including a lot of protégés andpeople that have trained under
Dr Peterson, so I think that isso important.
So, before we talk about ourmajor that's a great program.
Speaker 2 (05:59):
You know, I was just going to say the medical breast
program.
You know it providesdiagnostics, personalized team
and the team is wonderful andthey continue on with clinical
(06:26):
practice.
But I'm currently myself notpracticing.
Speaker 1 (06:32):
And I wondered if you wanted to talk a little bit
about Karis Eng.
Dr Karis Eng, an MD PhD.
She was certainly my sonStetson Thacker.
Dr Stetson Thacker, who's beenon our podcast, who's a PhD in
molecular medicines mentor, andI know she was a mentor to you
and so many people and shepassed last year.
Speaker 2 (06:56):
It was a rough year.
We lost both Dr Joseph Crow,who founded the Breast Center,
in February another medicalgiant and Dr Karis Eng in
October.
Both too soon and very, verysad losses.
But you know, for personallyand professionally they were
(07:17):
outstanding mentors and teachers, and scientists and physicians
and scientists and physicians.
Speaker 1 (07:32):
Yes, dr Crow I stood by him and Dr Alice Rim, in
charge of our breast imaging, in2002 when we opened our Center
for Specialized Women's Healthand really expanded upon not
just having breast services buthaving other specialty services.
And Dr Eng has won so manynational awards and made so many
original discoveries, so it'sreally quite a legacy, and we
certainly have, don't?
(07:52):
We have the world's leadingexperience in nipple sparing,
mastectomy and reconstruction.
Speaker 2 (08:00):
We do you know, our genetic and genomic program is
really unparalleled and theBreast Center, with its
multidisciplinary approach, hasreally been on the cutting edge
in many fields and certainly inthe field of nipple-sparing
mastectomy.
We probably have the largestsingle institution experience in
(08:23):
the world, you know,demonstrating the safety of
nipple sparing mastectomy evenin very high risk patients.
Speaker 1 (08:32):
And such wonderful outcomes.
And I even have some patientswho volunteer to come in and see
other patients who are thinkingabout this, to actually in the
exam room give them a littlelook about how wonderful the
cosmesis is.
So I think that for women whohave to deal with breast cancer,
(08:53):
so many of them can livecompletely full lives, not miss
a beat.
The therapies are so much moretargeted, outcomes are improving
and many women who are youngwomen go on and have children,
and women who don't want to havefurther children or are past
that stage in life or interestcan move into midlife and beyond
(09:17):
and expect to have the sametype of life as other women.
And so, since in the last 15plus years we've had increasing
research that shows thatmenopausal hormone therapy is
really the thing that we offerto midlife women that extends
life and reduces disease burden,and I've always been a
(09:39):
proponent of just because youmight have been unlucky enough
to have severe problems maybeneeding an organ transplant,
maybe having cancer, maybehaving had a heart attack or
serious blood clots, yeah, orvascular problems that those
(10:01):
women shouldn't be furtherdenied other common therapies.
So that gets us into usingmenopausal hormone therapy in
breast cancer survivors,something I've done for
essentially my whole career, butI think it's catching on a
little bit more, and I wantedyou to talk about it from your
(10:24):
breast perspective.
Speaker 2 (10:27):
You know I mean breast cancer is the most common
cancer in the United States andworldwide, aside from skin
cancer, and the good news is isthat treatments are improving
and mortality is improving inall different types of breast
cancer.
And it's important to rememberthat breast cancer is not just
(10:50):
one disease.
It's a group of entirelydifferent diseases that have
entirely different rates ofrecurrence and patterns of
recurrence and methods oftreatment and methods of
surveillance.
But what we do know we know acouple of things and you bring
(11:13):
to light very important pointsis that we have more and more
survivors and we have more andmore young survivors.
And we also know that mostwomen who have breast cancer
don't die from breast cancer.
They actually are more likelyto die from cardiovascular
(11:33):
disease or stroke.
And in women who are long-termsurvivors of breast cancer, we
have had a dogmatic approach inour multidisciplinary community
to absolutely not considersystemic menopausal hormone
(11:56):
therapy in a woman who's had ahistory of breast cancer due to
concern, and it's largely basedon theoretical concerns and not
actual medical data.
But we don't want to do any harmcommunity in terms of hormone
(12:23):
replacement following a breastcancer diagnosis.
But this question is far fromanswered and I think that you
know.
It's just fascinating thatyou've been taking women
individually, looking at theirpersonal risk for developing a
new cancer, their likelihood ofbeing at risk for developing
(12:49):
another cancer, looking at thetype of cancer that they had,
how they were treated, whetherthey responded well to treatment
and how far out they are fromtheir cancer.
And you've made the decision,the judgment call, in those
situations, with a womanunderstanding all of those
(13:10):
factors, she may choose, whenshe exhausts non-hormonal
methods of, you know,controlling menopausal symptoms,
to consider hormonal menopausalhormone therapy, to consider
hormonal menopausal hormonetherapy, and it really has.
You've been a trailblazer inthis field.
In fact, there was a recentstudy published by Dr Cheryl
(13:32):
Kingsberg at UH, who dida surveyof oncologists and oncology
patients and actually found youknow, in the real world about
15% of breast cancer survivorsin that cohort were currently
taking systemic menopausalhormone therapy.
(13:56):
So you're not alone, andhopefully you will be less alone
as time goes on if we're ableto answer these types of
questions.
Speaker 1 (14:07):
It's so interesting because I think that it's
twofold why there's been thishesitancy.
Well, it's probably threefold.
One, I think women tend to bemore anxious, and so if the
patient's projecting anxiety andthe physician or the clinical
team wants to do no harm, theypull back.
(14:28):
So part of it is the woman.
I think a second part of it hasto do with subtle ageism, in
that we accept risk for youngerwomen, for instance with
hormonal contraceptives whichhave a higher rate of blood clot
, and then we accept like hardlyany risk or zero risk with
(14:49):
menopausal hormones, andeverything has a risk Driving to
your doctor's office has a risk.
So this misunderstanding ofrisk, absolute and relative risk
is another factor, and the factthat we allow younger women who
have more life to live, toundergo therapies if they want
(15:14):
to control their reproductivelife, prevention of pregnancy.
But then at menopause, ifyou've lived long enough to lose
your hormones, we say oh, toobad, too bad, suffer.
And so I think that's a bigproblem.
And young women who've hadbreast cancer after their
treatment they can go on and getpregnant if they want to.
(15:35):
And that's way higher levels,much higher levels than what we
would ever do for menopause.
And so I think, having more ofthis perspective and also
understanding that the averageman who's older than a woman,
who's post-menopausal, has moreestrogen than she has.
(15:56):
How is that fair?
That's how I got involved inthis field, Because I just
thought it was so unfair.
And you're listening to theSpeaking of Women's Health
podcast.
I'm your host, Dr Holly Thacker, the Executive Director of
Speaking of Women's Health.
I'm at the Center forSpecialized Women's Health and I
run our Specialized Women'sHealth Fellowship.
And I am speaking to specialguest.
(16:17):
Dr Holly Peterson, who foundedour Medical Breast Program, is a
medical breast high-risk breastcancer expert and has done some
cutting-edge research.
And we're talking about safety,risk benefits, alternatives,
exceptions to menopausalhormones.
I want to talk a little bitmore, first about risk
(16:38):
assessment and your recentresearch.
Tell me about that combinedrisk score and what your
research found and how it's oneof the top 10 advances in
genomic medicine.
Speaker 2 (16:52):
Well, you are so funny.
I just love the way your brainworks.
I mean, you've brought up atleast 15 topics in that little
blurb there.
But you know, when you'retalking about risk, you need to
assess your own risk and we'lltalk about that but you need to
also, whenever you attend amedical visit, look at the risks
(17:18):
of doing something and look atthe risks of not doing something
, because that's actuallyrelevant here.
You mentioned that estrogen isthe most effective therapy for
menopausal symptoms.
We do know that women whoundergo early surgical menopause
(17:40):
or early iatrogenic menopauseMaybe what that means is we
cause the menopause, maybe byeither surgery or chemotherapy,
but those women we know are atrisk for early cardiovascular
disease and acceleratedosteoporosis, amongst other
(18:03):
things.
And so young women who undergoiatrogenic menopause at an early
age are certainly at higherrisk of those issues.
And so, while we need to worryabout estrogen per se but that's
(18:23):
debatable and we'll talk aboutthat we also need to be
cognizant that these young womenshould have estrogen in their
bodies and we may becontributing to cardiovascular
disease and osteoporosis bywithholding it in some
situations.
Now, in terms of riskassessment young women really
(18:50):
just a risk assessment is justto look at their family history
very carefully and look for redflags.
That might be a sign of, youknow, of hereditary syndromes,
but also just of being at higherrisk for breast cancer.
The things that we can all doare achieve and maintain our
ideal body weight and limitalcohol consumption.
(19:12):
But if there's a family historyof early breast cancer, say,
you know, under the age of 50,or ovarian or pancreatic cancer
at any age metastatic prostatecancer, multiple primary breast
cancers, male breast cancer, asyou brought up, Ashkenazi,
Jewish ancestry as there may bea one in 40 chance of carrying a
(19:36):
BRCA mutation, women need to beinherently aware that they may
be at much higher risk thananother woman.
Now that doesn't necessarilymean that they would not be
eligible for hormone therapy,for hormone therapy, either
(20:01):
contraceptive or menopausal, buta woman should know that she is
at a baseline higher risk.
When you talk about thecombined risk score or a way to
further substratify your riskthe youngest women we really
just ask about family history.
Then, when women get a littlebit older, say in their 30s, we
(20:22):
can use mathematical models likethe Tyra Kuzik model out of the
United Kingdom to furtherestimate their risk using
traditional risk factors.
But what we've added to that isadding your own genetics into
the mix, you know, becausethat's just a mathematical
(20:43):
calculation, and what we'velearned is that there are
essentially three layers ofgenetic testing, if you will.
There's the highly penetrantgenes like BRCA1 and BRCA2 and
PALB2.
There's also in that group thatare more rare CDH1, STK11, TP53
(21:07):
, and P10.
Those are all just alphabetsoup, but those are the real bad
genes and the most important ofthose are BRCA1, BRCA2, and
PALB2.
There's another level ofgenetic abnormality seen in
moderate risk genes such asCHECK2 or ATM, and the risk
(21:30):
that's conferred by those genesis similar to that of like.
If you have a benign biopsyshowing atypical hyperplasia,
it's not as much of a red flagas you might see with someone
who has triple negative breastcancer at age 35.
(21:51):
That might be a sign of BRCA1.
But many people carry these ATMand CHECK2 mutations.
They're not uncommon and theymay be causal.
But what we've discovered isthat there's a third level of
genetics that's kind of likenoise at the bottom.
There's over 300 singlenucleotide polymorphisms that
(22:13):
have been linked to breastcancer, that are independently
inherited from each parent, andso your complement of those 300
SNPs might be totally differentfrom a sibling of yours, and
that polygenic risk score, whichis a weighted aggregate of the
(22:37):
effects of those SNPs, whichneeds to be calibrated by
ancestry, gets prettycomplicated.
That polygenic risk score, incombination with the
mathematical risk model, canreally help to further
substratify women and what wefound is that in looking at
(22:59):
young Black women and youngHispanic women who develop
breast cancer, lo and behold, 50to 60% of those women had no
family history of breast orovarian cancer in a first or
second degree relative, buttheir polygenic risk score was
(23:20):
very different from even womenwho qualified for genetic
testing and were also black orHispanic but had negative
genetic testing and didn't getcancer.
So the ones who got breastcancer were very different in
terms of the polygenic riskscore from the ones who didn't
(23:41):
get cancer and this may changeour whole screening paradigm.
Ultimately, you know, we maystart looking at younger women
and offering them not onlygenetic testing for the highly
penetrant and moderatelypenetrant genes, but perhaps
even in the future, offeringthis test to see what women
(24:07):
might require more closesurveillance, say with breast
MRI.
So that's really what myresearch pertains to, not so
much with the question at handwith hormone in the breast
cancer survivor, but it isimportant for that survivor to
risk stratify.
(24:28):
I think that that's one of thefirst things a practitioner has
to think about when she'slooking at a breast cancer
patient who's contemplatinghormone therapy is what is her
level of risk?
And you can't use the riskmodels with breast cancer
patients because they're notdesigned for that.
(24:50):
However, the polygenic riskscore has been used
experimentally in severalstudies and predicts the
likelihood of developing a newcancer on the other side.
That's been shown in threeseparate studies, and so the
(25:10):
polygenic risk score cansubstratify risk in the general
population within a gene.
Say, if you had checked to, youcan check your polygenic risk
score to see whether you'rehigher or lower risk within that
genetic group.
It can be used to potentiallyidentify low risk women in the
(25:34):
long run, to potentiallyidentify low-risk women in the
long run, we're hoping.
But it also can help newlydiagnosed patients, not
currently in the clinicalsetting but in the research
setting, to identify their riskfor contralateral disease.
So it's very excitingtechnology.
You're going to see it in alldisease states.
It's not just breast cancer,it's not just cancer.
(25:55):
You're going to see it in heartdisease, diabetes.
These polygenic risk scores aregoing to help you to stratify
your risk in a lot of differentareas.
Speaker 1 (26:07):
That is so interesting.
Do you have any predictionsabout when you think that this
will be more standard practiceand recommended by the NCCN?
Speaker 2 (26:20):
So the validation studies date back to 2015.
We really have had solidvalidation studies for a very
long time, but the NationalComprehensive Cancer Network, or
NCCN, has concerns about whichPRS to use.
(26:43):
Some of them are not validatedin different ancestries because
these tests were originallydeveloped and validated in
Caucasian women of Europeandescent and the risk of these
different SNP alleles, thedifferent SNP DNA pieces, the
(27:07):
risk is different in differentancestries and so you have to
account for that and not all ofthe tests do.
The other issue is that manypractitioners don't really
understand how they would usethis going forward, and until
there are clear guidelines tohelp practitioners, help
(27:31):
patients, make those decisions,we're not going to see it in
clinical care.
You know, maybe in about, if Iwere to guess, three years or so
.
Three years or so althoughclinically they are available
but they're not recommended bygoverning bodies at this time.
Speaker 1 (27:54):
I have to say in my own experience, because years
ago, I mean before, weunderstood the benefits of
longevity with menopausalhormone therapy and post-Women's
Health Initiative, when therewas all this media on a
scientific study but kind ofnon-scientifically communicated
to the public, that caused a lotof anxiety where a lot of women
(28:17):
threw away their hormonetherapy.
I would regularly do the Galemodel or sometimes the Tyler
Cusick model and calculate howlong they had been on hormones.
We even offered for a point intime breast ductal lavage to see
if we saw atypical breast cells.
To try to encourage women forchemo prevention, because there
are agents that are approved.
To try to encourage women forchemo prevention because there
are agents that are approved totake to reduce your risk of
(28:40):
being diagnosed with breastcancer without any evidence
showing that it reduces deathrates.
But I found that kind of anunsatisfying type of practice
because some of the highest riskwomen I identified were not
interested in any kind ofpreventive treatment.
And so I think on a populationlevel yeah, for education.
(29:04):
Like people, women I think, areusually pretty invested in
having a pap smear to screen forearly cervical cancer and I
think more and more we're tryingto get to that 80% threshold in
adults over 45 to screen forcolon cancer, colorectal cancer.
I think most women are prettyaccepting of the mammogram and
(29:25):
breast imaging, which I know wehave differences of opinion in
imaging, just because I do seethe problem of over diagnosis
because then women don't wanthormone therapy or they stop
their hormone therapy.
Like I've got a patient comingin who's past the age that we
even do screening by theAmerican Cancer Society, but she
(29:47):
had to have her mammogrambecause she's so healthy,
because she's been on hormonesfor 35 years and of course
there's an abnormality, ofcourse there's a biopsy, it's
not cancer but you know she's atincreased risk, which of course
a woman of advanced age justage alone is at an increased
risk.
So when there's not really goodunderstanding, I don't think
(30:10):
amongst not just patients butpeople in the medical field
about what that risk actuallytranslates to.
It causes so much anxiety.
One thing that I do is,especially when I see a younger
woman who's diagnosed withbreast cancer, is there are
younger women who are notprevented from having their own
(30:31):
ovarian hormones, based on thetype of cancer or it being
estrogen negative.
Or maybe they've undergonetherapy that stopped their
period for a while but then theyresumed ovarian function and
they continue to have their ownhormones until the age of
menopause.
And then they go into menopauseand then they think they can't
have hormones, even though theyjust had it for the last 10
(30:54):
years.
Or I see women who may be inmenopause but they saved some
embryos and they got pregnantbecause they wanted to be a mom.
They had really high estrogenlevels for nine months and felt
terrific and then postpartum iftheir ovaries didn't start
working again, which many timesis the case.
(31:14):
All of a sudden, horrible hotflashes and the women don't even
want to accept local vaginalestrogen, which we offer to
women, even undergoing activebreast cancer treatments if
needed.
So I wondered if you had anyperspective on that.
Speaker 2 (31:30):
On those next 10 questions.
All right, I'm going to startwith the sensitivity of
screening mammography in elderlywomen.
There have been no studies ofmammography in women over the
age of 75.
And major radiologicassociations like the American
College of Radiology, becausethe sensitivity is so good when
(31:52):
the density goes down, most ofthe you know of the prominent
experts in that field feel thatprobably it's okay to continue
mammography till 90.
Speaker 1 (32:06):
I know you're going to kill me, but don't, don't
don't start now I want to, Iwant to address some of your
other questions, so you know,and I think that's fine if women
do that, but I just don't wantthem coming crying to me when
they're told that they can't beon hormones anymore.
(32:28):
And they have zero symptoms andwe can't tell them that it's,
that it's not a false positive.
Speaker 2 (32:35):
Yeah.
Speaker 1 (32:35):
Yeah.
Speaker 2 (32:36):
Yeah, you know, and there are fewer false positives
in the older women but anywayslet's return to our topic, which
you know you.
You know so much about thehistory of the women's health
initiative study and whathappened with that, and I'm
going to try to summarize it ina brief way.
(32:56):
But you know, when did youstart at the clinic, holly I?
Speaker 1 (33:03):
joined the staff in 1990.
, 1990.
Speaker 2 (33:08):
Okay, I came in 1997.
And so we were both really in onthe beginning of all of this.
You know, in the early 90s Ithink it was 1992 when the
Women's Health Initiative studystarted you know, the largest
study in women ever performed,$700 million or so where really
(33:29):
the question was to answerwhether menopausal hormone
therapy reduced the risk ofcardiovascular disease.
And so, rather than choosing theappropriate age of women to
really answer hormonal questionsthey included the majority of
women were over the age of 60,smokers, overweight.
(33:53):
They were really looking at adifferent question, and in 2002,
the study was suddenly stoppedbecause there were big media
releases that there was a 26%increase in breast cancer risk
(34:13):
with hormone replacement therapy, as it used to be called, and
what they didn't talk about, asyou mentioned initially, was the
increase in absolute risk thatthat may confer to a woman.
Risk at the age of 50 is 1.3%or 1.5% over the next five years
(34:42):
.
If she increases her risk overthe next five years by 26%, she
goes from a whopping 1.5% to a1.7% or 8%, which most women
will accept in terms of absoluteincrease in risk.
If this had been explained in2002, I don't think that we
(35:07):
would be sitting and having thisdiscussion in 2024.
And, in fact, what they show-2025,.
Speaker 1 (35:15):
We're in 2025.
Speaker 2 (35:17):
2025,.
Oh no, you're going to send mychecks back.
No, so it's fascinating becausein 1994, a paper was published
saying estrogen replacementtherapy in breast cancer
survivors.
It's time to look at this.
(35:38):
This was in 1994.
And many trials started lookingat this question would it be
okay to consider hormonereplacement in breast cancer
survivors?
And unfortunately, most ofthose trials were stopped.
When the Women's HealthInitiative trial was stopped
(36:00):
because everyone was nervousabout continuing several
prospective studies which failedto accrue the appropriate
number of patients and reallydidn't answer the questions that
(36:21):
they set out to answer, andwe're now making clinical
decisions without the data thatwe need.
I think that the most importantpart of this question is that
we need further study in thisarea, but what we do know is not
(36:44):
as ominous as most people think, and I wanted to kind of go
over that with you.
So you know, one thing is thatwe allow women who have invasive
breast cancer, that's estrogensensitive, to stop their
(37:04):
hormonal therapy, theirendocrine therapy, their
tamoxifen or aromatase inhibitortherapy, in order to have a
baby and breastfeed.
And that's a very high hormonalstate to have a baby and
breastfeed and that's a veryhigh hormonal state.
You were mentioning that.
We allow them, you know thatopportunity, or encourage it,
following their treatment.
(37:25):
We actually allow it in themidst of their treatment.
Speaker 1 (37:29):
And those women have been shown, yeah, to do.
Speaker 2 (37:32):
Well, you know.
And the other group that youknow is reassuring is the
patients with the highlypenetrant gene mutations,
patients with BRCA1 and BRCA2,who are at very high risk when
we recommend that they havetheir tubes and ovaries removed
because there's no goodscreening for ovarian cancer.
(37:55):
We have been giving routinelymenopausal hormone therapy back
to those women and have notshown an increased risk of
breast cancer.
Those are the highest riskwomen that you're going to find.
Women who do not have a geneticmutation, who have survived
(38:16):
breast cancer, have about a 0.4%per year chance of having
another breast cancer develop,and so it's very, very low and
most people don't realize that.
But if they do have a geneticmutation, of course their
(38:37):
likelihood, if they retain theirbreast tissue, is higher.
But you know the treatments arebetter.
Women are more likely to becured of this disease.
You know we do give estrogen.
You know we allow high estrogenstates like pregnancy, even in
the midst of cancer treatment,and the BRCA population
(39:02):
tolerates menopausal hormonetherapy very well following
their risk-reducing surgery, andwe give it to the time of
natural menopause in women whohaven't had breast cancer.
Perhaps we should be givingthat longer, and that's another
question that I have in terms ofthese women, but you brought up
(39:22):
what about the woman with ERnegative disease or breast
cancer that does not express theestrogen receptor?
Would it be okay, in thosewomen who have invasive breast
cancer that's estrogen negative,to consider hormone replacement
(39:43):
therapy earlier?
My argument is no.
I want to go over the differenttypes of breast cancer and
their typical recurrencepatterns and rates.
Dcis or ductal carcinoma insitu, which is stage zero breast
(40:09):
cancer, it's just stage zerothe potential to well, I believe
it's breast cancer, but that'sa different.
That's a different if you don'tundergo radiation.
(40:33):
There's about a 30% localrecurrence rate and 15% and 50%
of those are invasive.
So it's hard for me to notclassify it in the cancer you
know category when you haveinvasive recurrences occurring
50% of the time.
But anyways, distantrecurrences are very rare less
than 2%.
So a woman who is several yearsout from a DCIS diagnosis, you
(40:56):
know is very different from awoman who has has stage two ER
positive disease, you know, whois in the midst of therapy and
there's everything in between.
So there's triple negativebreast cancer and HER2 positive
breast cancer which usuallyoccur, recur, if they're going
(41:19):
to recur in the first five yearsand typically in the first
three years.
And so a woman who's five yearsout from ER negative breast
cancer or HER2 positive breastcancer, you know, is in a good
place.
We don't have data thathormone's okay, but we know that
(41:42):
she's in a good place in termsof her breast cancer diagnosis.
With estrogen sensitive, her2negative breast cancer the tail
for recurrence goes out muchfurther and those women need to
understand that they might havea recurrence completely
(42:04):
unrelated to hormone replacementor no hormone replacement
because of their originaldisease.
But let me tell you somethingabout ER negative disease that
bothers me in terms of saying,oh, it must be okay because it
doesn't contain estrogenreceptors.
Women with BRCA1 mutations whohave triple negative breast
(42:31):
cancer and have their ovariesremoved in the first year have a
markedly improved survival rateas compared to women with
triple negative breast cancerand BRCA1 who have their ovaries
removed much later, and thatmakes me worry a little bit.
(42:55):
There's something, and it maynot be the estrogen, but there's
something about the absence ofthe ovary that is promoting
better breast cancer survival,and so there's something about
that that gives me pause aboutestrogen replacement right away.
(43:17):
Now, you know, five years in it,you know, with a triple
negative breast cancer it's acompletely different discussion.
But I don't think that one canjust assume that if it's
estrogen receptor negative, it'sokay, because there are.
There are just different thingsthat we've found.
(43:38):
For instance, there's anAmerindian snip that's found in
the Hispanic population that isprotective from breast cancer.
What it does is it lowersestrogen levels and lowers
(43:59):
breast density, but it preventstriple negative disease, you
know.
And so there's a lot about thatthat we don't understand, and
so I do have a little hesitationwhere many people don't because
of those issues.
(44:19):
You know, a patient with DCISor who's five years out from
triple negative disease or HER2positive disease, or a person
who's ER positive, HER2 negative, who's doing very well and has
a very low likelihood ofrecurrence and is five years out
, you know, those are thepatients I believe that we
(44:40):
should start with and be talkingto and be enrolling in clinical
trials.
Speaker 1 (44:48):
So this has just been such an excellent discussion
and we'll have to bring you backon Dr Peterson and maybe even
have you guest host for me,because you call yourself the
other Dr Holly, so that would bewonderful.
Speaker 2 (45:04):
Oh, I'd love to do that.
Speaker 1 (45:06):
It's great to get other perspectives of really
experienced clinician scientists, scholars and leaders
scientists, scholars and leaders.
I would mention to ourlisteners who are physicians and
clinicians that we have asection on
speakingofwomenshealthcom undertools for physicians, including
links to CME, including links tomenopausalearningorg, where we
(45:32):
have some lectures that youcould view of a breast
oncologist talking about the useof hormone therapy in breast
cancer survivors, as well asheart disease and many other
topics.
So thank you to our listenersand to Dr Peterson for joining
us on the Speaking of Women'sHealth podcast.
(45:53):
Please subscribe on ApplePodcasts, spotify or tune in or
wherever you listen.
Share the podcast, give us afive-star rating and I hope
you'll tune in for futureepisodes.
Remember be strong, be healthyand be in charge.
Thank you.
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