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Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers.

van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, Van't Veer LJ, Tollenaar RA - Br. J. Cancer (2005)

Bottom Line: Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO).After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant.The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, D6-44, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

ABSTRACT
The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I-IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

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Overall survival in patients who opted for CPM vs patients who remained under surveillance.
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fig3: Overall survival in patients who opted for CPM vs patients who remained under surveillance.

Mentions: In order to examine whether CPM prevented death from breast cancer, breast cancer-specific and overall survival were compared between the CPM and the surveillance group. The mean follow-up did not differ markedly between both groups, 3.4 vs 3.7 years, respectively (Table 3c). Most women in both groups died of breast cancer (Table 3a and c). Breast cancer-specific survival (including the first breast cancers) was not significantly better in the CPM group (log rank, P=0.11) (Figure 2). However, these were mostly related to the first breast cancer as only one of them (in the surveillance group) had developed a contralateral breast cancer. Therefore, it was not possible to evaluate contralateral breast cancer-specific survival. A significant overall survival advantage was observed in the CPM group compared to the surveillance group (log rank, P=0.027) (Figure 3) due to three additional events: two ovarian and one lung cancer. Multivariate Cox's proportional-hazards analysis showed that, after adjustment for BPO (and time between first breast cancer and start follow-up and chemotherapy treatment), women in the CPM group did not significantly have better survival than those under surveillance (overall mortality HR 0.35, P=0.14) (Table 4). Patients who underwent BPO had significantly better breast cancer specific (HR 0.15 (95% CI 0.04–0.51), P=0.003) and overall survival (HR 0.14 (95% CI 0.05–0.41), P<0.0001) than patients who did not undergo BPO. In multivariate analysis, with adjustment for CPM, time between first breast cancer between first breast cancer and start follow-up and chemotherapy, the breast cancer-specific survival was no longer significant (HR 0.28 (95% CI 0.07–1.11), P=0.07), while the impact of BPO on overall survival remained (HR 0.23 (95% CI 0.07–0.78), P=0.018). Having opted for both CPM and a BPO resulted in a significantly better survival than surveillance only (overall mortality HR 0.12 (0.03–0.46) and breast cancer-specific mortality HR 0.16 (0.04–0.61), both adjusted for time between first breast cancer and start follow-up and chemotherapy).


Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers.

van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, Van't Veer LJ, Tollenaar RA - Br. J. Cancer (2005)

Overall survival in patients who opted for CPM vs patients who remained under surveillance.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361560&req=5

fig3: Overall survival in patients who opted for CPM vs patients who remained under surveillance.
Mentions: In order to examine whether CPM prevented death from breast cancer, breast cancer-specific and overall survival were compared between the CPM and the surveillance group. The mean follow-up did not differ markedly between both groups, 3.4 vs 3.7 years, respectively (Table 3c). Most women in both groups died of breast cancer (Table 3a and c). Breast cancer-specific survival (including the first breast cancers) was not significantly better in the CPM group (log rank, P=0.11) (Figure 2). However, these were mostly related to the first breast cancer as only one of them (in the surveillance group) had developed a contralateral breast cancer. Therefore, it was not possible to evaluate contralateral breast cancer-specific survival. A significant overall survival advantage was observed in the CPM group compared to the surveillance group (log rank, P=0.027) (Figure 3) due to three additional events: two ovarian and one lung cancer. Multivariate Cox's proportional-hazards analysis showed that, after adjustment for BPO (and time between first breast cancer and start follow-up and chemotherapy treatment), women in the CPM group did not significantly have better survival than those under surveillance (overall mortality HR 0.35, P=0.14) (Table 4). Patients who underwent BPO had significantly better breast cancer specific (HR 0.15 (95% CI 0.04–0.51), P=0.003) and overall survival (HR 0.14 (95% CI 0.05–0.41), P<0.0001) than patients who did not undergo BPO. In multivariate analysis, with adjustment for CPM, time between first breast cancer between first breast cancer and start follow-up and chemotherapy, the breast cancer-specific survival was no longer significant (HR 0.28 (95% CI 0.07–1.11), P=0.07), while the impact of BPO on overall survival remained (HR 0.23 (95% CI 0.07–0.78), P=0.018). Having opted for both CPM and a BPO resulted in a significantly better survival than surveillance only (overall mortality HR 0.12 (0.03–0.46) and breast cancer-specific mortality HR 0.16 (0.04–0.61), both adjusted for time between first breast cancer and start follow-up and chemotherapy).

Bottom Line: Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO).After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant.The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, D6-44, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

ABSTRACT
The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I-IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

Show MeSH
Related in: MedlinePlus