At High-Risk for Breast Cancer? Your Options
Breast cancer kills thousands of women every year around the world. It is generally a disease of older women; the average age at diagnosis is 64 years. About 12% of women develop breast cancer at some time in their lives.
Most women have no early warning. Instead, the diagnosis is made on a regular physical examination or during scheduled screening.
About 10% of women do know their cancer risk in advance. Breast cancer in a close family member prompts a genetic study, which reveals their risk. There are no easy choices, but this knowledge offers the opportunity to avoid this dreadful disease.
Two recent developments are of enormous significance:
- We’ve learned which gene mutations are associated with an increased risk for the development of breast and other cancers.
- Genome sequencing and genetic analysis have become widely available and relatively affordable.
Just Some Facts
In 2020, 2.3 million women were diagnosed with breast cancer. It claimed 685,000 lives.
One in seven women diagnosed with breast cancer has a close relative (mother, sister, or daughter) with breast cancer. That means most women who develop breast cancer have no family history to forewarn them.
Hereditary breast and ovarian cancer (HBOC) is associated with variants of the BRCA1 and BRCA2 genes. HBOC makes up 15-25% of these cancers.
Breast Cancer Prediction
Before we discovered the gene mutations, we knew some factors associated with a high probability of developing breast cancer.
- Family history. Breast cancer in a sibling, mother, or child.
- Familial cancer syndromes.
- Radiation therapy to the chest.
- Early start to menstruation and late menopause. Prolonged exposure to hormones is the probable reason.
Several gene mutations are associated with a high risk of breast cancer.
The most infamous are mutations of the BRCA1 and BRCA2 genes. Women with the BRCA1 mutation have a breast cancer risk of 72% by age 80 years; the risk is 69% for BRCA2 mutations. These mutations are also associated with a higher risk of ovarian cancer.
Genes associated with a greater than 50% lifetime risk of developing breast cancer are the PTEN, TP53, STK11, CDH1, and PALB2 genes. Many of these are involved in the familial cancer syndromes.
Other genes associated with breast cancer risk are the BARD1, RAD51C, RAD51D, ATM, CDH1, NF1, MSH6, and CHEK2 genes. Women with thesegene mutations have a higher lifetime breast cancer risk than average, but less than 50%.
Radiation Therapy to the Chest
Radiation to the chest is a component of the treatment of several childhood cancers such as Hodgkins’ lymphoma, leukemia, bone tumours, and kidney cancer.
Radiation is a risk for breast cancer. Increased cancer risk appears by approximately eight years after the radiation therapy. Higher amounts of radiation, as used for Hodgkin’s lymphoma and Wilm’s tumor, are associated with higher risks of breast cancer.
The risk for women treated before the age of 30 is significant. Their risk of developing breast cancer by the age of 50 is over 50%.
The risk is increased further if anthracycline drugs (like doxorubicin or daunorubicin) were used in the treatment of the childhood cancer. On the other hand, radiation of the ovaries reduces the risk of breast cancer. This is probably because of reduced estrogen exposure of radiation damaged breast cells.
Familial cancer syndromes
These syndromes carry an inherited predisposition for developing breast cancer. We’ve known about these syndromes for a long time, but have unraveled the genetics recently.
Testing all women with breast cancer is crucial. It helps with treatment decisions, prediction about cure and recurrence, and prevention of other cancers. It also aids in cancer prevention for family members.
The Li-Fraumeni syndrome (TP53 gene mutation). This syndrome runs in families. People with mutations of the TP53 gene develop cancer of the breast, bones, brain, stomach, blood, and other organs. Almost every affected person develops cancer. Women with this gene variant should start breast cancer screening as early as 20 years.
The Cowden syndrome (PTEN gene mutation). Apart from breast cancer, this syndrome is associated with cancers of the skin, brain, mucous membranes, thyroid, and endometrium. The lifetime risk of breast cancer is 25-50%.
The Peutz-Jeghers syndrome (STK11 gene mutation). Apart from other manifestations, this syndrome is associated with cancers of the breast, stomach, intestines, and ovaries.
The hereditary diffuse gastric cancer syndrome. This is a syndrome of stomach cancers that runs in families; 20-40% of affected people have a mutation of the CDH1 gene. Women with this syndrome have an increased risk of breast cancer, too.
Cancer of One Breast
Does it increase the risk of cancer on the other side? It’s an important matter. Many women choose to have both breasts removed to reduce the risk of future cancer.
Removing the healthy breast reduces the risk of new cancer on that side.
It does not reduce the risk of recurrence or spread (metastasis) of the original cancer.
Only women with other risk factors (genetic or familial) should consider the option of removing the other breast as a precaution. Women without such risk factors have a low probability of new cancer, and the benefits of such surgery are probably insignificant.
Breast Cancer High Risk: The Options
- Risk reducing mastectomy.
- Screening with mammography and magnetic resonance imaging.
- Bilateral risk‐reducing salpingo‐oophorectomy.
Risk Reducing Mastectomy
Removing healthy breast(s) surgically to prevent cancer is called risk-reducing mastectomy (RRM). As its name suggests, it reduces the risk of cancer and early death because of cancer.
The removal of both breasts to preempt any cancer occurring is called bilateral RRM.
When cancer is diagnosed in one breast, and the other is also removed to prevent cancer, it is called contralateral RRM.
These are drastic procedures with lifelong body image and cosmetic effects. Such decisions need meticulous consideration of individual cancer risks and must be a joint decision between doctor and patient.
Types of Risk Reducing Mastectomy
Total or Simple Mastectomy. Removal of the breast, nipples, areolae, and much of the skin over the breasts.
Nipple-sparing mastectomy. Removal of the breast tissue while preserving the nipples, areolae, and most of the skin overlying the breasts.
Skin sparing mastectomy. Removal of the breasts, nipples, and areolae, but preserving most of the skin.
Most women choose to combine RRM with breast reconstruction surgery. Nipple-sparing mastectomy is associated with the best cosmetic results and no higher risk of breast cancer than the other two procedures.
Why Risk Reduction Mastectomy?
Because risk elimination isn’t possible.
Elimination of the risk of breast cancer isn’t possible because even meticulous surgery cannot remove all breast tissue. Surgically removing both breasts reduces the risk of breast cancer by more than 90%. A small probability of breast cancer remains even after this drastic measure.
When a woman chooses contralateral RRM, the risk of new cancer in the healthy breast is almost eliminated. However, the risk of recurrence of the original cancer and of metastasis (spread of the cancer to other organs) remains.
Problems with Risk Reduction Mastectomy
- Immediate problems: complications of anesthesia, bleeding, infection, or additional surgery for complications
- Body image issues
- Sexual relationship issues
- Emotional and mental health problems.
Who Should Opt for Risk Reduction Mastectomy
- Women with one of the gene mutations that carry a high risk of breast cancer. Their risk of breast cancer increases after age 25 years; this is when they should consider bilateral RRM.
- Women who have these gene mutations and opted for screening or medication and develop cancer in one breast. Opting for contralateral RRM (removal of the healthy breast and the one with cancer) reduces the risk of new cancer.
- Women who received chest wall radiotherapy before the age of 30 years.
Women who have gene variants that put them at moderate risk for breast cancer should not opt for surgery. Screening and chemoprevention are reasonable options for them.
Contralateral RRM is not recommended for women with moderate or average risk who develop cancer in one breast.
Breast Cancer Screening
Breast cancer screening is recommended for women with no special risk factors, and saves lives among them (Read also: Breast Cancer Screening: Saving Women’s Lives). It is even more valuable for women at high risk for breast cancer.
Women at high risk should start annual screening by magnetic resonance imaging (MRI) as early as age 25. They should add annual mammography at age 30, scheduling them six months apart.
MRI and mammography each detect tumors missed by the other. For women at high risk, it is best to use both for the early detection of cancers.
Two types of drugs, called cancer prevention agents (CPAs) are used to prevent breast cancer in women at high risk.
Selective estrogen receptor modulators (SERMs): tamoxifen and raloxifene.
Aromatase inhibitors: exemestane and anastrazole.
These drugs, taken daily, reduce the occurrence of cancer. The current recommendation is to use a CPA for five years.
We have the most experience with tamoxifen. It reduces the occurrence of breast cancer in women at high risk for it. Women of all ages can use this drug. This drug needs caution; women taking it have higher than average occurrences of uterus (endometrial) cancer and blood clots.
The other SERM, raloxifene, is less effective at preventing cancer, but also has lesser adverse effects.
Exemestane and anastrazole also reduce breast cancer occurrence. No direct comparison with tamoxifen is as yet available, but they are probably more effective at preventing breast cancer over five years of daily use.
The adverse effects profile of these drugs is different from the SERMs—gastrointestinal (diarrhea, nausea), hormonal (hot flashes), fractures, or joint pains. Thus, they are significantly safer than the SERMs.
Though not considered prevention, the chemotherapy used to treat one-sided breast cancer reduces the occurrence of cancer in the other breast.
Risk-Reducing Bilateral Salpingo-Oophorectomy (RRBSO)
This is the removal of the ovaries and fallopian tubes to reduce the risk of cancer in these organs. The genes that increase breast cancer risk, particularly BRCA1 and BRCA2, also increase the risk for these cancers.
RRBSO is an option for women that have completed their families. When done, it reduces the probability of breast cancer also by as much as 50%.
Spontaneous menopause before the age of 40 years also protects against breast cancer. Estrogen deprivation is the probable reason for these effects.
Which Strategy is Best?
It’s a deeply personal decision. Every woman told she is at increased risk for breast cancer should decide for herself, with the advice of her doctor and other experts.
Surgery (bilateral RRM) seems a sound option. Increased risk of breast cancer begins around the age of 25 years; removing both breasts at this time will prevent 90-95% of cancers.
Reducing cancer risk prolongs life and lessens anxiety substantially. However, it is major surgery, and there are emotional and psychological effects.
Screening is an alternative, and we know it detects cancer early and saves lives. Women at average risk get mammography every two years or one year. Women with heightened risk should get MRI and mammography annually. By staggering the two, these women execute cancer screening every six months.
Chemoprevention sounds attractive. Taking an oral drug seems simple compared to major surgery or frequent visits to the MRI/mammography clinic. Sadly, we have no evidence that these drugs have a benefit in terms of prolonging life. There is also some worry that tamoxifen is less effective against estrogen receptor-negative breast cancers, which are more likely in younger women and BRCA1 mutation carriers.
It’s not necessary to choose one of the methods and remain cemented to it. Switching between them as per the requirements of her life stage is the right of every woman.
For instance, a woman of twenty might be screened for gene mutations because of a family history of breast cancer. Identification of a BRCA1 mutation need not mandate immediate RRM.
This young lady can opt for regular screening for ten years. Having completed her family and breastfed her children, she could then proceed for surgical removal of both breasts, ovaries, and Fallopian tubes.
Cancer is terrible, and we can’t wish it away. Avoiding cancer needs some effort to identify risk, and hard decisions afterward.
Science has provided us with dependable tools to predict cancer in some women. Breast cancer treatment is getting better all the time, but women still die of it.
Using clues provided by family members who had breast cancer, women can identify their own risk. While there are no easy ways forward for those at high risk, making the right choices can avoid a dreadful disease, eliminate much anxiety, and prolong life.
Basu et al. Contralateral Risk-Reducing Mastectomy: Review of Risk Factors and Risk-Reducing Strategies.
Carbine et al. Risk-reducing mastectomy for the prevention of primary breast cancer.
Dorling et al. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women. Breast Cancer Association Consortium.
Hu et al. A Population-Based Study of Genes Previously Implicated in Breast Cancer.
Jatoi I, Kemp Z. Risk-Reducing Mastectomy. JAMA. 2021
Jatoi. Risk-Reducing Options for Women with a Hereditary Breast Cancer Predisposition.