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Breast Cancer 101
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BRCA GENE MUTATIONS
In 2013, we expect 232,340 new invasive breast cancers plus 64,640 in situ
(pre-invasive) cancers, and 40,030 deaths; 2240 of those cancers will be in men
with 410 deaths. We also expect 22,240 ovarian cancers to be diagnosed this
year, and 14,030 deaths.
Only 5-10% of breast cancers and 14% of ovarian cancers occur from a genetic
predisposition, which means a mutation inherited from either parent allows
cancer to grow uncontrolled. The most common genetic mutation for which we can
test is called, BRCA (pronounced, brack’-uh), and was discovered in the early
1990s.
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BRCA MUTATION QUICK FACTS
* BRCA stands for BReast CAncer. Normal BRCA genes help you fight cancer when
it happens in your body. Some families carry mutated or broken BRCA genes
that can be passed down from one generation to the next.
* Women carrying a BRCA mutation have up to an 87% lifetime chance of breast
and 54% chance of ovarian cancers (vs. general population: 12% breast and <
1% ovarian).
* While these risks seem staggering (and they are!), a woman’s risk is never
that high on any given day in her life. The following table (from King,
et.al.) stratifies the risks of getting breast and ovarian cancer by decade
of life, and compares those risks to the general population for breast
cancer:
Risk Gen Popn BRCA1 BRCA1 BRCA2 BRCA2
by age (breast) (breast) (ovarian) (breast)
(ovarian)
30 0.06% 3% 0.00 0.06%
0.00
40 0.46% 21% 3% 17%
2%
50 1.86% 39% 21% 34%
2%
60 4.26% 58% 40% 48%
6%
70 7.66% 69% 46% 74%
12%
80 11.36% 81% 54% 85%
23%
* Men can inherit this mutation, and their breast cancer risk is up to 8% (vs.
1 in 1000 general population), with a 20% chance of prostate cancer (vs.
14% general population).
* BRCA-2 is associated with other cancer risks: prostate, melanoma, and
pancreatic. (To date, increased colorectal cancer risk has not been
established, but is suggested by some studies.)
* In those BRCA-1 carriers who get breast cancer, 85% will have a more
aggressive “triple negative” subtype (vs. 15% general population).
* Only 5-10% of breast cancers and 14% of ovarian cancers occur from a genetic
predisposition – the rest do not.
* General population risk for a BRCA mutation is 1 in 500 people, but those of
Ashkenazi Jewish heritage are 1 in 40
* An estimated 19 million people in the U.S. have family histories of breast
and ovarian cancer that meet the US Preventive Services Task Force criteria
for hereditary cancer testing; that means they have a > 5-10% chance of
carrying the gene mutation. As of this year, only 1% have tested. If all
19 million tested, around 1 million would be found to carry the BRCA gene
mutation.
* Testing is done by an oral rinse or simple blood draw and can be done in the
convenience of your own home with the Color Hereditary Cancer Test.
The Cancer-Kicking! Summit is now available digitally to stream
Over 11 hours of video content are now available to stream from any device. If
you cannot attend our annual Summit at Terranea Resort, sign up for the Virtual
Summit instead and get the same information from the in-person Summit in the
convenience of your own home.
Tell Me More
8 RED FLAGS THAT INDICATE A POSSIBLE BRCA MUTATION
To assess your personal risk for a BRCA mutation, take this simple Genetics Quiz
1st, 2nd, or 3rd degree relatives – from maternal or paternal sides –
with breast cancer before age 50 or ovarian cancer at any age;
Ashkenazi Jewish heritage (Ashkenazis are Eastern European Jewish from Germany,
Poland, Lithuania, Ukraine and Russia, as opposed to the Sephardic Jewish
population primarily from Spain, parts of France, Italy, and North Africa);
Any male relative with breast cancer;
Any relative who is a known BRCA mutation carrier (the child of a carrier has a
50% chance of inheriting the mutation);
Breast cancer in self prior to age 50;
Two breast cancers in self, any age;
“Triple negative” breast cancer in self;
Two or more family members with breast, ovarian, pancreas, prostate, melanoma,
uterine, colon, and stomach cancers (this flag also captures possible non-BRCA
inherited genetic mutations associated with breast or ovarian cancer).
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INSURANCE AND PRIVACY CONCERNS
* The Health Insurance Portability and Accountability Act of 1996 (“HIPAA”)
made it illegal in the United States for group health plans to consider
genetic information a “pre-existing condition” or to use it to deny or limit
coverage. HIPAA imposes federal penalties for breaches of medical
confidentiality.
* The Genetic Information Nondiscrimination Act (“GINA”) of 2008 protects
people in both group and individual health plans from genetic discrimination.
It makes it illegal for employers to use genetic information in the hiring,
firing, job assignments, and promotions of their employees. GINA also
prohibits health insurance companies and employers from requesting or
requiring an individual to take a genetic test.
* To date, no evidence of life insurance discrimination following BRCA1 and
BRCA2 testing has been found.
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MANAGEMENT OPTIONS FOR BRCA CARRIERS
PLBC’S APPROACH: When first meeting a woman newly diagnosed with a BRCA
mutation, our immediate goal is to learn as much about her preconceptions and
personality as possible. How has the cancer experience of affected relatives or
friends colored her perception of treatments and side effects? Is she
heterosexual, lesbian, or both? Is she in a stable relationship, married, or
single? Has she completed childbearing? If no, does she desire children? Is
breastfeeding a strong priority? Do we need to discuss freezing eggs or embryos
if she is between 30-40? How much do her breasts “mean to her” in terms of body
image, sense of sexuality, sexual pleasure, and defining her femininity. Which
at-risk organ creates more anxiety for her: breasts or ovaries, and why?
Two main strategies exist for BRCA carriers: surveillance and surgery.
Surveillance involves a combination of imaging and exams, as well as possibly
taking risk-reducing medications.
Surgical interventions require removing the organs as risk, namely, the breasts
and ovaries.
* Breast & Ovarian Surveillance
PLBC’S BRCA plan for women: Beginning at age 18, or 10 years younger than the
youngest relative with breast cancer, every 3 months, you have breast imaging or
an exam. An example plan follows:
* Month 1 = Mammogram (wait until 30 years old); Whole breast screening
ultrasound (begin at 18).
* Month 4 = Clinical breast exam with a breast specialist.
* Month 7 = Breast MRI, timed to menstrual cycle days 7-10 (begin at age 25;
day 1 is the day bleeding starts); Contrast Enhanced Spectral Mammography
CESM for those who cannot have an MRI.
* Month 10 = Clinical breast exam with a breast specialist.
* Every month = Self breast exams (cycle days 7-10). If you don’t know how to
do a self breast exam, please watch our how-to video.
For those who prefer twice-a-year surveillance, we combine the imaging with
clinical breast exams, and meet every 6 months.
Ovarian surveillance begins at age 30, or 10 years prior to youngest relative
with ovarian cancer, and includes the following:
* Transvaginal Pelvic ultrasound every 6 months (cycle days 1-10)
* CA-125 blood marker testing every 6 months (after cycle day 5)
* Pelvic exam by gynecologist every 6 months
PLBC’S BRCA-2 Additions:
* At 35, get an annual MRI of the pancreas, along with blood levels for liver
function and pancreatic enzymes.
* At 25, begin annual skin and eye exams for melanoma.
PLBC’S BRCA plan for men:
* At 35, clinical breast exam annually
* At 35, self breast exams monthly
* At 40, baseline mammogram
* At 40, prostate and yearly PSA checks.
* BRCA-2 additions as above.
* Risk Reduction Medications AKA Chemoprevention
* Oral contraceptives (birth control pills)
* Reduce the risk of ovarian cancer up to 60%. Reduction increases with
duration of use.
* Do not seem to increase breast cancer risks in BRCA1/2, but some studies
suggest a breast cancer increase with OCPs used in women prior to first
pregnancy.
* Tamoxifen
* An anti-estrogen pill that blocks estrogen receptors throughout the body
* Once diagnosed with breast cancer, Tamoxifen decreases breast cancer in the
opposite breast in both BRCA-1/2 by 50%
* Reduces first time breast cancer risk in BRCA-2 (not BRCA-1) by up to 62%
(NSABP-P1 study)
* Side effects – menopause symptoms: hot flashes, night sweats, decreased
libido, vaginal dryness, mood swings (see Menopause Miracle to counteract
these symptoms)
* Complications – blood clots, stroke, uterine cancer
* Prophylactic Operations
* Prophylactic (“Preventive”) Bilateral (“Double”) Mastectomy
* Definition of “Prophylactic”: Acting to defend against or prevent something,
especially disease; protective.
* Prophylactic mastectomy reduces future breast cancer risk to less than 10%,
but with a truly excellent mastectomy technique, the risk should be under 2%,
even when keeping the nipples.
* What is the ideal age? 10 years younger than the youngest affected relative
with breast cancer; or between ages 30-40; or earlier per patient desire. Why
the 10 years advice? Scientific studies show that the doubling rate of a
cancer cell is such that the first cell most likely mutated 5-8 years before
the cancer could ever be detected and diagnosed. So, the 10 years is meant
to stop cancer before it starts.
* New Technique #1: At the Pink Lotus Breast Center, as well as in many of our
colleagues’ practices, gone are the days of a “slash” across the entire
chest, or an unrealistic “grapefruit” attached to the chest, meant to
resemble the sloping beautiful breast that was once in its place. Minimally
visible incisions using Nipple-sparing, Areolar-sparing, and Skin-sparing
choices, as well as diverse oncoplastic techniques available today can leave
a woman feeling sexy and strong inside her own skin.
* New Technique #2: A Nipple Delay procedure should be considered whenever the
nipples are thought to be at high risk for either disease or insufficient
blood supply after a planned nipple-sparing mastectomy. The delay, performed
1-2 weeks prior to the actual mastectomies, uses the planned mastectomy
incision and lifts half of the skin off of the breast surface. Also, a small
disc of the tissue directly behind the nipple and areola is removed and
analyzed by a pathologist. This procedure rules out disease in the breast
ducts directly behind the nipples, which would make nipple preservation
dangerous. Additionally, a nipple delay recruits extra blood flow to the
nipple and skin, lessening the chances of nipple and skin loss due to
insufficient blood supply after mastectomy. Since starting this technique in
2008, my loss of skin and nipple after mastectomy has decreased to < 2%.
* New Technique #3: Whenever a breast contains cancer and the armpit lymph
nodes cannot be felt on exam, we routinely perform a sentinel node biopsy,
which is removal of the first nodes receiving the breast lymphatic drainage –
in this way, we find out if cancer spread beyond the breast. The chances of
finding cancer in a breast removed prophylactically range from 2-8%. Until
now, a woman undergoing prophylactic mastectomy had two choices: (1) take the
sentinel node(s) in case cancer is found in her breast, or (2) don’t take the
node(s). This dilemma has been resolved with my new technique, called
Prophylactic Breast Dye Injection. PBDI allows the node to be identified,
but not removed, giving more control and peace of mind to women.
* Reconstruction options vary depending on your desired aesthetic outcome, body
habitus, general health, prior breast operations, and radiation exposures.
The two broad categories of reconstruction include implants and flaps.
* Implants are the most common reconstruction, often requiring two stages,
whereby a tissue expander is placed prior to the final implant. A tissue
expander is a deflated implant that goes behind the pectoral muscles and gets
slowly inflated with saline over a period of 2-3 months, until the desired
volume is reached. A second operation is performed to swap the expander for
the final implant (usually silicone). In “one-step” implant operations, the
final implant is placed at the time of mastectomy. Newly FDA-approved
anatomic implants are teardrop shaped, appear more natural than the
traditional round ones, and ripple less. Allograft and synthetic sheets of
material are sometimes used to create a more natural look, to make up for
weak and thin body tissues, and to build an additional layer between the
implant and skin.
* Autologous Flaps use your own skin, fat and sometimes muscle from the
abdomen, back (latissimus), thigh (gracilis), or buttock to create a
potentially more natural breast reconstruction than implants can achieve.
Flaps, however, create scars at the donor site, potential weakness in the
donor area, and involve a longer operation than implants, with longer
hospital stays and recovery periods.
* Nipple reconstruction is an option for those whose nipples are removed at the
time of mastectomy. Either the breast skin itself, or a graft of skin from
elsewhere on the body, is used to create a projecting nipple (no sensation).
Tattoos can be surprisingly realistic recreating a tinted areola (the
pigmented circle around a nipple).
* Prophylactic Bilateral Salpingo-Oopherectomy (BSO)
* Prophylactic BSO reduces future ovarian cancer (primary peritoneal cancer)
risk to 1-2%.
* What is the ideal age? 10 years younger than the youngest affected relative
with ovarian cancer; or by age 40; or earlier per patient desire; or as soon
as childbearing is finished. Why the 10 years advice? Scientific studies
show that the doubling rate of a cancer cell is such that the first cell most
likely mutated 5-8 years before the cancer could ever be detected and
diagnosed. So, the 10 years is meant to stop cancer before it starts.
* Consider freezing eggs or embryos between ages 30-40. Eggs are not
fertilized, and contain just the woman’s half of a future baby, whereas
embryos contain both egg and sperm united. This option is ideal for the
woman who wants to have a BSO, but for a number of possible reasons, is not
ready for pregnancy. She can preserve viable eggs/embryos, undergo BSO, and
implant an embryo into her intact uterus when ready for motherhood.
* Controversial to be sure, Preimplantation Genetic Diagnosis (PGD) allows a
BRCA carrier the chance to notpass on his/her genetic mutation. PGD analyzes
embryos (obtained by IVF techniques) for the BRCA mutation, allowing only
those without the mutation to be implanted into the uterus. A word of
caution to any couples who both carry a BRCA-2 mutation: there is a 25% of
creating a child with two faulty BRCA-2 genes, called Fanconi anemia. These
children live a life fraught with medical issues and early death.
* Prophylactic BSO can be performed laparoscopically. Since the majority of
the cancer risk lies in the part of the fallopian tube away from the uterus
and toward the ovary, it is considered safe to keep the uterus. The chances
of incidentally finding cancer in prophylactic BSO tissues ranges from 2-26%.
* Taking hormone replacement therapy (HRT) after BSO does not increase breast
cancer risk in BRCA1 or BRCA2 mutation carriers.
* Performing BSO prior to mastectomies reduces breast cancer risk up to 68%;
however, studies show no reduction in breast cancer risk if BSO is done after
age 50.
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CONCLUSION
No single management strategy can be universally recommended to BRCA1 and BRCA2
mutation carriers. Decisions depend on the unique life circumstances of each
woman: her personal experiences, her dreams and goals, her “essence”, values,
and convictions. At the Pink Lotus Breast Center, it is our job, and our
privilege, to present clear information about risk, and to explain how together,
we can reduce that risk. Our deepest hope is to replace anxiety with answers,
and fear with confidence. The ultimate plan, of course, is to save lives.
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BRCA, Gene Mutation, Hormones, Insurance, Mastectomy, MRI, Prophylactic, Risk
Factors, Risk Reduction, Surgery, Surveillance
Dr. Kristi Funk
Dr. Kristi Funk is board-certified breast cancer surgeon, women's health
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methods for all types of breast disease and also a recognized leader of the
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Power Up and also hosts the Cancer-Kicking! Summit and the Cancer-Kicking!
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Jiewen Zhuang
11 years ago
I had done the test BRCA in China and have found BRCA1-R1443X mutation. What
percentage do you think I would get breast cancer or ovarian cancer? As Julie
said she had 87% of breast cancer and 50% of ovarian cancer. What test should i
do to found the percentage? If I do the operation in you hospital, how much is
the estimated overall cost?
i am 51 years old, and my sister just past because of the breast cancer. My
mother died of ovarian cancer. So I might get genetic inheriting.
Thanks very much!
0
0
Alison
Reply to Jiewen Zhuang
5 years ago
Jiewen Zhuang , I know I’m five years late to this discussion but I hope you’re
still around. You cannot take a test to find out the percentage. A genetics
counselor can help you determine that percentage, however with your sister
having had BC and your mom having OC and you being a carrier of the brca
mutation…it is very likely that you WILL get cancer. I pray that you saw a
doctor in time and took all the preventative measures. <3
0
0
33andCounting
11 years ago
I was diagnosed in my early thirties with locally metastatic advanced stage
breast cancer. I had two kids before thirty, breast fed and lived a healthy
lifestyle. I knew I had a family history of breast cancer (my grandmother had
breast cancer twice and her mother died of ovarian cancer). I shared this
information with all of my doctors, but was never offered BRCA testing until
after I was diagnosed with cancer. Turns out I do have the BRCA mutation. I
never even knew about this test until I was diagnosed. I am glad this is being
brought to public… Read more »
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