Efficacy of risk-reducing mastectomy (RRM) on overall survival (OS) in BRCA1/2-associated breast cancer (BC) patients

Reporter: Saumil Gandhi, MD PhD
The Abramson Cancer Center at the University of Pennsylvania
Ultima Vez Modificado: 7 de junio del 2013

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Presenter: Bernadette Anna Maria Heemskerk-Gerritsen, MSc
Presenter's Affiliation: Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, Netherlands

Background

  • Up to 10% of all breast cancers are associate with inherited mutations.
  • The majority of hereditary breast cancers are associated with mutations in BRCA1 or BRCA2 gene.
  • These genes are inherited in an autosomal dominant pattern and markedly increase the risk of developing breast cancer with a lifetime risk of 50 to 85%.
  • In women with BRCA1/2 mutations who develop breast cancer, the risk of developing contralateral breast cancer ranges from 10 to 20 percent at 5 years compared to 1 to 3 percent in those with sporadic breast cancer.
  • The risk of developing a contralateral breast cancer is also higher with younger age at diagnosis of the initial breast cancer.
  • In BRCA1/2 mutation carriers with unilateral breast cancer, RRM of the contralateral breast significantly reduces the risk of developing a contralateral breast cancer.
  • However, whether RRM of the contralateral breast improves OS is not known. The authors aim to answer this question with a prospective study of a Dutch multicenter cohort.

Methods

  • The effect of RRM on contralateral breast cancer incidence and OS was studied in a multicenter cohort consisting of 515 breast cancer patients with BRCA1/2; (399 BRCA1, 116 BRCA2).
  • 177 BRCA1 and 48 BRCA2 carriers underwent RRM.
  • A Cox analysis was performed with RRM as a time dependent variable.
  • Women contributed person-years of observation (PYO) to the control group from the date of primary breast cancer diagnosis or DNA diagnosis (whichever came last) to the date of death, RRM, or last contact. Women contributed PYO to the RRM group from the date of RRM until date of death or last contact.

Results

  • There were no significant differences in size, nodal status, differentiation grade, receptor status, and endocrine therapy between the control and RRM group.
  • Median age of primary breast cancer diagnosis was slightly lower for women that received RRM versus control group (38 years versus 42, p<0.001).
  • Median time period between primary breast cancer and RRM was 2.3 years (range 0.02-20.1).
  • Women receiving RRM were also more likely to get risk-reducing salpingo-oophorectomy (81% versus 67%; p<0.001). However, the incidence of ovarian cancer was not significantly different between the two groups.
  • With a median FU of 11.7 years after primary breast cancer diagnosis, 58 contralateral breast cancers were observed in control women, while 4 cases occurred in the RRM group. The calculated incidence rates (per 1000 PYO) were 30.6 for control group versus 2.5 for RRM group (HR 0.09, 95% CI 0.03-0.24).
  • 45 women died during 2408 PYO in the control group compared to 17 women during 1756 PYO in the RRM group. The calculated mortality rates (per 1000 PYO) were 18.9 for control group versus 9.7 for RRM group (HR 0.56, 95% CI 0.32-0.99).
  • 10 year OS was 80% for the control and 90% for the RRM group (p=0.008).

Conclusions

  • RRM improves the incidence of contralateral breast cancer and overall survival in BRCA1/2 mutation carriers with unilateral breast cancer.

Clinical Implications

  • While many retrospective studies have examined the role of RRM in reducing the risk of contralateral breast cancer, this is a prospective study of a large multicenter cohort with long follow-up that shows a survival benefit with RRM.
  • One of the weaknesses of the study is that fact that there was no data recorded for whether women underwent total or skin sparing mastectomies.
  • Furthermore, a significantly higher percentage of women in the RRM group received systemic therapy compared to the control group (66% versus 50%). This difference may account for the improved OS in the RRM group.
  • A prospective randomized study is needed to determine whether contralateral breast RRM confers a survival benefit in BRAC1/2 carriers with breast cancer.

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