Guidance for Women with Gene Abnormalities

About 10% of all breast cancers are associated with an inherited genetic abnormality. And the most common genetic abnormalities involve BRCA1 and BRCA2.

Cancers that are associated with abnormalities of BRCA1 and BRCA2 genes are, in some ways, similar to each other and to other types of cancers, and in other ways, different:

• An abnormality in BRCA2 tends to be more "laid back" than in BRCA1. The overall risk of getting breast cancer in your lifetime if you have a BRCA1 or BRCA2 abnormality is between 50% and 85%. But a BRCA1 abnormality tends to carry a slightly higher risk.
• Breast cancers in women with BRCA1 abnormalities are more likely to be estrogen-receptor negative and to have "high-grade" cell growth. Both of these characteristics mean that chemotherapy will be more effective than hormonal (anti-estrogen) therapy in treating these cancers.
• Overexpression of the HER2/neu cancer gene is not commonly found in either BRCA1 or BRCA2 cancers. However, another abnormality involving a gene called p53 is more likely to be present in women with BRCA1 or BRCA2 abnormalities:
  • 40% of women with a BRCA1 abnormality have increased p53 levels.
  • 27% of women with a BRCA2 abnormality have increased p53 levels.
• Women with BRCA1 or BRCA2 gene abnormalities have no greater risk than other women of having multiple cancers in the same breast when their breast cancer was diagnosed.
• Women with DCIS are just as likely to have inherited gene abnormalities as those with invasive cancer.

When a woman with a breast cancer gene abnormality develops a breast cancer, she needs to consider two important things:

1. treating the diagnosed cancer with an effective and appropriate combination of surgery, radiation, and chemotherapy
2. reducing the risk of potential future breast cancer and ovarian cancer. Women with breast cancer and a BRCA1 abnormality have a significantly greater future risk of developing breast cancer and ovarian cancer. Women with a BRCA2 abnormality have a significantly greater future risk of developing breast cancer, and in some families, ovarian cancer

Decisions about cancer treatment

These guidelines provide reassurance that the combination of lumpectomy and radiation is as effective as mastectomy in women with a breast cancer gene abnormality in the following situations:

• a single breast cancer is identified
• the tumor is completely resected (that is, the tumor is removed with clear margins of resection)

Decisions about prevention of future cancers

The latest research offers these insights:

1. Once you are finished having children, preventive or prophylactic ovary removal in women with BRCA1 accomplishes 2 important goals: it reduces ovarian cancer risk by 50–80% (statistics vary, depending on the study), and it reduces the risk of breast cancer by 50–70% (again, statistics vary by study).
2. For cancers linked to abnormal breast cancer genes, the type of abnormal breast cancer gene a woman has seems to influence how much risk reduction she gets from prophylactic ovary removal. A 2008 study by researchers at Memorial Sloan-Kettering Cancer Center found that in women who had an abnormal BRCA1 gene, removing the ovaries was more beneficial for lowering ovarian cancer risk than lowering breast cancer risk. In women who had an abnormal BRCA2 gene, removing the ovaries was more beneficial for lowering breast cancer risk than ovarian cancer risk.
3. If you have BRCA1 or BRCA2 and you want to prevent the onset of a new breast cancer (whether you’ve never had breast cancer or you have had the disease), then preventive or "prophylactic" breast removal can reduce this risk by 85–90%. This is an important risk reduction, because after a diagnosis of one breast cancer in a woman with a genetic abnormality, the risk of her getting a new breast cancer is approximately 3% every year (for example, 15% over 5 years). Without BRCA1 or BRCA2, the risk of developing a new breast cancer after one episode of breast cancer is only 1% per year.
4. Tamoxifen (which had already been proven to reduce breast cancer risk in women without BRCA1 or BRCA2) is likely to be just as effective in women with a gene abnormality, based on results from the Breast Cancer Prevention Trial. This study showed that tamoxifen reduced breast cancer risk by 45% in young women with a significant family history of breast cancer (who are most like to have an inherited gene abnormality). And although it was not reported as part of the findings, researchers believe that a separate analysis of the women with BRCA1 or BRCA2 in this study will further confirm the value of tamoxifen.

Conclusions for you

Careful review of these preventive options with your doctor is essential, in order for you to make an informed and comfortable decision. Keep these points in mind:

1. Your first and most important consideration is to effectively treat the breast cancer that you were diagnosed with. Prevention of a future breast cancer is a separate but related issue.
2. If you have BRCA1 and you choose a prophylactic ovary removal after you’re finished having children, then you are already protecting yourself from both breast and ovarian cancer. Let’s suppose your risk of developing a new breast cancer is 50% over the course of your lifespan. If prophylactic ovary removal reduces that risk by approximately 60%, then you’re down to a 20% remaining risk (when you take away 60% of a 50% risk, you have 20% left). If tamoxifen reduces that 20% risk by 45%, then you have a remaining risk of 11% (take away 45% of the 20% remaining risk, and you’re left with an 11% risk). And if you are taking care of yourself and having regular mammograms and careful breast examinations, then you’re increasing the odds that any possible breast cancer will be found as early as possible, when it is most curable. So, if you take all of the above actions to reduce your risk, is prophylactic mastectomy necessary?

Let’s look at the numbers again. Mastectomy can reduce breast cancer risk by nearly 90%. If you start with the same 50% risk of breast cancer and reduce that 50% by 90%, you are left with a 5% risk. But you can also shrink your risk (to 11%) in ways that may not feel as extreme.