Women who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer.
Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers.
The risk of subsequent contralateral breast cancer in carriers is markedly increased.
Mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer.
The option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy.
Among BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation is associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset.
For women who are born with a germ-line mutation in BRCA1/2, the risk of developing breast cancer is approximately 70% and the risk of ovarian cancer is 20%–40% during their lifetime.
Breast tumors of BRCA mutation carriers tend to develop at a young age, and bilateral disease is more common than in sporadic cases.
Current recommendations for the management of BRCA mutation carriers advocate intensified screening by clinical breast examination, mammography, ultrasound and annual breast magnetic resonance imaging (MRI) starting before age 30, prophylactic removal of the ovaries with fallopian tubes at age 35–40 years after completion of childbirth and consideration of risk-reducing bilateral mastectomies.
Prophylactic bilateral mastectomy effectively reduces the risk of breast cancer in BRCA mutation carriers and is considered for primary prevention by healthy carriers as well as carrier patients who already have developed breast cancer.
As mastectomy is a disfiguring procedure that may significantly impair quality of life many BRCA carriers do not opt for this procedure.
The risk of ipsilateral breast cancer recurrence following breast conserving therapy was comparable between BRCA mutation carriers and non-carriers.
The risk of subsequent contralateral breast cancer in BRCA carriers is markedly increased, reported to be as high as 25%–30% over 10 years and more than 40% over 15 years, as compared with 3% and 7%, respectively, in non-carriers.
Notably, for BRCA-carrier patients who had breast conserving treatment, the risk of subsequent cancer in the ipsilateral breast was approximately 15% over 10 years, which is lower than in the contralateral intact breast, and this risk reduction is attributed to irradiation of the affected breast.
Bilateral salpingo-oophorectomy and possibly tamoxifen reduce both ipsilateral and contralateral breast cancer in carrier patients that undergo breast conserving therapy.
The choice of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment including surgery and irradiation to the involved side, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy.
At a median follow-up of 58 months (range 10–121 months), 10 patients (12.4%) developed contralateral breast cancer in the control arm within a median of 32 months (range 7–106 months), as compared with 2 patients (2.5%) in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation.
Mastectomy of the diseased breast along with risk reducing contralateral mastectomy is often advocated for BRCA carriers who are treated for early breast cancer.
Many carrier patients forego this option for fear of its harmful effects on their lives and choose breast-conserving surgery rather than bilateral mastectomy as their definitive surgery.
It is demonstrated that prophylactic irradiation of the contralateral intact breast, in addition to standard loco-regional treatment of the affected side, significantly reduced the risk of subsequent contralateral breast cancer in BRCA carrier patients who declined contralateral mastectomy.
The 2.5% contralateral cancers in irradiated breasts developed after a long delay, 80 and 105 months following prophylactic irradiation, as compared with 12.4% contralateral breast cancers in non-irradiated contralateral breasts that developed at a median of 32 months.
These results are comparable to risk-reducing contralateral mastectomy in BRCA mutation carriers.
In another study 1 of 75 (1.3%) carrier patients who had prophylactic contralateral mastectomy developed contralateral breast cancer as compared with 6 of 43 (14%) in the surveillance group, at a mean follow-up of 3.5 years(Van Sprundel).
Metcalfe found that among 146 BRCA carrier patients who had contralateral prophylactic mastectomy 1 developed contralateral breast cancer at a median follow-up of 9.2 years, compared with 97 of 336 (29%) carrier patients whose contralateral breast was intact.
Neither hypersensitivity nor increased toxicity was noted in BRCA mutation carriers when therapeutic doses of radiation were delivered to the breast and no increase in subsequent malignancies was reported.
There was no added risk of contralateral breast cancer from scatter radiation at 10 and 15 years.
BRCA mutation carriers are increased among patients with radiation-associated angiosarcoma, with an estimated approximately twofold non-significant increase in the risk of radiation-associated sarcoma .
In BRCA mutation carriers radiation-associated sarcoma is a rare event in carriers as in the general population and should not be considered in the choice of radiation treatment of them.
With a median follow-up of nearly 5 years, prophylactic irradiation of the contralateral breast yielded an 80% reduction of breast cancer and delayed its onset (32 versus 92 months).
The risk of contralateral breast cancer is significantly increased, reported as high as 25–30% over 10 years and 40% over 15 years, as compared to 3% and 7% respectively in non carriers.
Prophylactic bilateral mastectomy effectively reduces the risk of breast cancer in these women, however, this mutilating surgery is not acceptable for many of them.
For BRCA mutation carriers who already developed breast cancer, breast conservation, comprising of lumpectomy followed by whole breast radiation, id not associated with increased risk of ipsilateral breast cancer recurrence as compared with non carriers (10-15% over 10 years), especially if they also underwent prophylactic oophorectomy.