Most inherited cases of breast cancer are associated with one of two abnormal breast cancer genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). Women with an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70. Women with an abnormal BRCA1 or BRCA2 gene who have been diagnosed with disease also have a higher risk of developing a new, second breast cancer compared to women who don't have an abnormal breast cancer gene. Women with an abnormal BRCA1 or BRCA2 gene also have a higher-than-average risk of ovarian cancer.
Two studies are reviewed here. These results were presented at the 2010 European Breast Cancer Symposium.
The first study compared surgery options for 655 women with an abnormal BRCA1 or BRCA2 gene who had been diagnosed with breast cancer:
The women were followed for about 8 to 9 years.
Survival rates were the same no matter which type of surgery the women had.
Still, women with an abnormal BRCA1 or BRCA2 gene who had lumpectomy plus radiation were between 4 and 5 times more likely to develop another breast cancer (either the same cancer coming back or a new breast cancer) in the same breast compared to women with an abnormal BRCA1 or BRCA2 gene who had mastectomy. But when the women who had lumpectomy plus radiation also had chemotherapy after surgery, their risk of developing another breast cancer was about the same as the women who had mastectomy.
Based on the results, the researchers suggested that lumpectomy plus radiation therapy could be a good choice for women with an abnormal breast cancer gene, but only if chemotherapy is included in the treatment plan.
After a breast cancer diagnosis, women with an abnormal breast cancer gene also may consider removing the other healthy breast, called contralateral prophylactic mastectomy. Research has shown that contralateral prophylactic mastectomy lowers the risk of breast cancer developing in the healthy breast. In the second study reviewed here, the researchers looked at whether contralateral prophylactic mastectomy lowered the risk of developing metastatic breast cancer (breast cancer that has spread outside the breast area to another part of the body) or helped improve survival rates in women with an abnormal breast cancer gene.
The researchers followed 390 women with an abnormal breast cancer gene who had been diagnosed with breast cancer for about 6 years:
In this study, contralateral prophylactic mastectomy didn't lower the risk of developing metastatic breast cancer and also didn't improve overall survival in women with an abnormal breast cancer gene.
Still, it's important to remember that other research has shown that contralateral prophylactic mastectomy lowers the risk of developing a new breast cancer in the healthy breast.
If you have an abnormal breast cancer gene and have been diagnosed with breast cancer, you and your doctor need to consider the risks associated with an abnormal breast cancer gene as well as the specific characteristics of the cancer and your preferences as you develop your treatment plan.
Lumpectomy plus radiation may be a good choice for you, but the first study reviewed here suggests that chemotherapy also should be part of your treatment plan.
Deciding to have the healthy breast removed also may make sense for you as you try to do all you can to reduce your future risk. Still, you may want to talk to your doctor about ALL of your risk reduction options. Contralateral prophylactic mastectomy is only one of these options and is a very aggressive step. While it may be the right decision for you, give yourself the time you need to consider your decision carefully. Prophylactic mastectomy doesn't have to be done at the same time as lumpectomy or mastectomy. Together, you and your doctor can make the decisions that are best for you and your unique situation.
BARCELONA (MedPage Today) -- Women with mutation-related breast cancer lived just as long with breast-conserving surgery as they did with mastectomy, data from longitudinal clinical studies showed.
Survival curves were virtually superimposable out to 20 years, when breast cancer-specific survival was almost 90% among patients with BRCA-related breast cancer treated with radical or conservative surgery.
But local failure occurred almost five times as often with breast-conserving surgery, Lori Pierce, MD, of the University of Michigan reported here at the European Breast Cancer Conference.
Nonetheless, those local recurrences did not translate into an increased risk of metastatic recurrence.
Moreover, the local recurrence rate with breast conservation plummeted with adjuvant chemotherapy, such that the difference from mastectomy was no longer significant.
"Increased local failure after breast-conserving therapy did not translate into increased systemic recurrence at 15 years or a reduction in breast cancer-specific or overall survival," Pierce said.
Referring to the eight-year median duration from treatment to local failure, Pierce added, "While these findings could be due to limited statistical power, they could also be the result of the development of new primaries, rather than true recurrences as breast events.
Carriers of BRCA1/2 mutations have as much as an 85% lifetime risk of developing breast cancer and as much as a 50% lifetime risk of second primary breast cancers. Because the BRCA1/2 genes are involved in DNA double-strand break repair and maintenance of genomic integrity, questions have arisen about the wisdom of treating the cancers with breast-conserving surgery plus radiation therapy, which results in DNA double-strand breaks, Pierce said.
Several studies have shown that prophylactic mastectomy reduces breast cancer risk by 90% or more in BRCA1/2 carriers, she continued. However, only scant published data relate to outcomes of BRCA-related breast cancer treated by mastectomy. The lack of data have raised the question of whether breast-conserving therapy might be comparable to mastectomy with respect to local control, breast cancer-specific survival, and overall survival.
To address the comparability issues, Pierce and colleagues retrospectively analyzed data on 655 women with BRCA-related breast cancer treated at centers in the U.S., Australia, Israel, and Spain.
The patient population consisted of 302 patients treated with breast-conserving surgery plus radiation therapy and 353 treated with mastectomy (103 of whom also had radiation therapy). Median follow-up was 8.2 years in the breast-conservation group and 8.9 years in the mastectomy group.
The data showed that the rate of local recurrence in the breast conservation group increased from 4.7% at five years to 10.5% at 10 years, 23.5% at 15 years, and 30.2% at 20 years. The comparative rates in the mastectomy group were 1.4%, 3.5%, 5.5%, and 5.5% (P<0.0001).
Patients in both groups had prolonged failure-free intervals, a median of 7.8 years with breast conservation and 9.4 years in the mastectomy group. Moreover, 70% of local failures in the breast-conservation group involved a different breast quadrant, a different histologic type, or both.
"This suggests, but is not conclusive, that most of the recurrences are, in fact, new primary cancers," said Pierce.
The multivariate analysis showed that breast-conserving therapy increased the risk of local failure as first failure more than four-fold compared with mastectomy (HR 4.5, 95% CI 2.3 to 8.9, P<0.0001). The analysis also showed a dramatic difference in the risk of local failure depending on whether a patient had chemotherapy after breast-conserving surgery: no increased risk for patients who received adjuvant chemotherapy versus a hazard ratio of 5.4 for patients who did not (95% CI 2.3 to 13.3, P=0.0001).
Upon grouping breast-conservation patients by chemotherapy status, Pierce and colleagues found that patients who did not receive adjuvant chemotherapy had a local failure rate of 43.7% at 15 years and 53.2% at 20 years. That compared with 10.7% at both intervals for patients who received adjuvant chemotherapy, a difference that no longer differed significantly from mastectomy group (P=0.082).
The findings from the study show that mastectomy with or without radiation therapy is effective for BRCA-related breast cancer, said invited discussant Thomas Bucholz, MD, of M.D. Anderson Cancer Center in Houston. Breast-conserving therapy is a "reasonable short-term option," but not by itself.
"Prevention strategies are important with breast conservation," said Bucholz. "Consideration might be given to chemotherapy, which possibly results ovarian ablation. Surgical ovarian ablation is another possible option."
A second study -- this one from Dutch researchers but also reported here -- showed that contralateral prophylactic mastectomy failed to improve survival in women with BRCA-mutation cancer.
Mastectomy effectively reduces the risk of recurrence in BRCA carriers, but the impact on distant recurrence and survival was unclear, said Annette Heemskerk-Gerritsen, of Erasmus University Medical Center in Rotterdam, the Netherlands.
To examine benefits beyond local recurrence, investigators reviewed medical records of 390 patients with a history of BRCA-related unilateral breast cancer, 138 of whom had undergone mastectomy. After a median follow-up of six years, the mastectomy and non-mastectomy groups had distant disease-free survival (expressed as incidence rates) of about 25 per 1,000 person-years. Incidence rates for overall survival were about 25 per 1,000 person years for the non-mastectomy group and slightly, but not significantly, lower in the mastectomy group.
Incidence rates for breast cancer-specific survival were slightly less than 25 per 1,000 person-years among patients who did not have prophylactic mastectomy compared with a little less than 20 per 1,000 person-years in the mastectomy group, also a nonsignificant difference.
"Overall, risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer does not result in improved survival," said Heemskerk-Gerritsen.
Neither Pierce nor Heemskerk-Gerritsen had any disclosures.
Primary source: European Breast Cancer Conference Source reference: Pierce L, et al "Local therapy options in BRCA1/2 carriers with operable breast cancer: the importance of adjuvant chemotherapy" EBCC 2010; Abstract 7N.Additional source: European Breast Cancer ConferenceSource reference: Heemskerk-Gerritsen BAM, et al "Is risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer beneficial with respect to distant disease free survival and overall survival?" EBCC 2010; Abstract 500.
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