BRCA1/2 Mutations Linked with Better Outcome in Triple-negative Breast Cancer

According to the results of a small study, approximately 20% of women with triple-negative breast cancer are carriers of a BRCA1 or BRCA2 gene mutation. Triple-negative breast cancer patients with these mutations appear to have better survival than patients without these mutations. These results were recently presented at the 2010 Breast Cancer Symposium.[i]

Some breast cancers display different characteristics that require different types of treatment. The majority of breast cancers are hormone receptor-positive, meaning that the cancer cells are stimulated to grow by exposure to the female hormones estrogen and/or progesterone. These cancers are typically treated with hormonal therapy that reduces the production of these hormones or blocks their effects.? Other cancers are referred to as HER2-positive, which means that they overexpress the human epidermal growth factor receptor 2, part of a biologic pathway that is involved in replication and growth of a cell. HER2-positive breast cancers account for approximately 20-25% of breast cancers and are treated with agents that target the receptor to slow growth and replication.

Triple-negative breast cancer refers to cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options. Research is ongoing to determine prognostic factors such as gene mutations that may impact prognosis and help to individualize care.

In the current study, researchers from the M. D. Anderson Cancer Center evaluated the frequency and effects of BRCA1 and BRCA2 gene mutations among 77 women with triple-negative breast cancer. Inherited mutations in these genes can be passed down through either the mother’s or the father’s side of the family and greatly increase the risk of breast and ovarian cancer.

15 of the 77 patients (20%) had a BRCA1 or BRCA2 mutation. Five-year relapse-free survival was 86% for patients with a BRCA mutation compared with 52% for patients without a BRCA mutation.

The researchers concluded that triple-negative breast cancer patients with BRCA mutations experienced a significantly lower recurrence rate. These findings were unexpected because previous studies had not shown a difference in recurrence rates.

Patients with triple-negative breast cancer may wish to speak with their healthcare team regarding the risks and benefits of genetic testing.

It should be noted that other studies have not found as high a rate of BRCA mutations in women with triple negative breast, so it is possible that the results of this study represent an overestimate.

[i] Gonzalez-Angulo M, Chen H, Timms K, et al. Incidence and outcome of BRCA mutation carriers with triple receptor-negative breast cancer (TNBC). Presented at the 2010 Breast Cancer Symposium, Washington, DC, October 1-3, 2010. Abstract 160.

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Phase III Trial Fails to Find Benefit of PARP Inhibitor for Triple-Negative Breast Cancer

In a Phase III clinical trial, the addition of the PARP inhibitor iniparib to chemotherapy did not improve outcomes among women with metastatic triple-negative breast cancer. These results—which differ from those of a prior Phase II clinical trial—were presented at the 2011 annual meeting of the American Society of Clinical Oncology.??

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.??

Iniparib belongs to a class of drugs called PARP inhibitors. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Because many triple-negative breast cancers are thought to have defects in DNA repair, researchers have hypothesized that triple-negative breast cancers may be particularly vulnerable to PARP inhibition.???

A Phase II clinical trial provided hope that iniparib would indeed provide a valuable new treatment option for triple-negative breast cancer. Results published in the New England Journal of Medicine early in 2011 suggested that the addition of iniparib to chemotherapy with GemzarR (gemcitabine) and carboplatin delayed cancer progression and improved overall survival.?[1] Median overall survival was 7.7 months among women treated with chemotherapy alone and 12.3 months among women treated with chemotherapy plus iniparib.?

?A subsequent Phase III clinical trial, however, did not find a benefit. The study enrolled a larger group of women (519 versus 123 in the Phase II trial), and once again compared chemotherapy alone with chemotherapy plus iniparib for the treatment of metastatic triple-negative breast cancer. According to results presented at the 2011 annual meeting of the American Society of Clinical Oncology, the addition of iniparib did not significantly improve overall or progression-free survival.?[2] ?

Although the Phase III results were a great disappointment, it remains possible that iniparib could still provide a benefit to women whose cancer has progressed (worsened) on other treatments. Researchers are continuing to explore whether there are particular subsets of women who respond well to this treatment.?

References:?

[1] O’Shaughnessy J, Osborne C, Pippen JE et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. New England Journal of Medicine. 2011;364:205-214.?

[2] O’Shaughnessy J, Schwartzberg LS, Danso MA et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). Presented at the 2011 annual meeting of the American Society of Clinical Oncology. Chicago, IL. June 3-7, 2011. Abstract 1007.?

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Breast-Conserving Therapy May Outperform Mastectomy Alone for Women with Early-Stage Triple-Negative Breast Cancers

For women with early-stage triple-negative breast cancer, treatment with breast-conserving surgery plus radiation therapy may result in fewer cancer recurrences in or near the breast than mastectomy without radiation therapy. These results were published in the Journal of Clinical Oncology.???

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.???

For women with small breast cancers that have not spread to the lymph nodes, treatment often includes breast-conserving surgery (lumpectomy) plus radiation therapy or mastectomy (removal of the entire breast) without radiation therapy. These two approaches are generally thought to produce similar outcomes, but it’s possible that for certain subtypes of breast cancer one approach may be more effective than the other.?????

To compare breast-conserving therapy (lumpectomy plus radiation therapy) to mastectomy among women with early-stage (T1-2N0) triple-negative breast cancers, researchers evaluated information from 468 patients. The group was fairly evenly split in terms of how many had been treated with breast-conserving therapy and how many had been treated with mastectomy without radiation therapy.???

Study participants were followed for a median of 7 years. One of the outcomes of interest was locoregional recurrence. This refers to a recurrence of the cancer in the breast, chest wall, or nearby lymph nodes.???

Five-year survival without a locoregional recurrence was 96% among women treated with breast-conserving surgery and 90% among women treated with mastectomy without radiation therapy. In other words, women treated with breast-conserving therapy had a lower risk of recurrence in the breast, chest wall, or lymph nodes than women treated with mastectomy without radiation therapy.?At the time of the analysis, overall survival was similar in the two groups.?

Although additional studies are needed, it’s possible that adding radiation therapy may improve outcomes among women who undergo mastectomy for early-stage, triple-negative breast cancer. In the current study, the risk of recurrence within or near the breast was lower among women treated with breast-conserving therapy (lumpectomy plus radiation therapy) than among women treated with mastectomy without radiation therapy.????

Reference: Abdulkarim BS, Cuartero J, Hanson J et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. Journal of Clinical Oncology. Early online publication June 13, 2011.?

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