Biglia Nicoletta, D'Alonzo Marta, Sgro Luca G, Tomasi Cont Nicoletta, Bounous Valentina, Robba Elisabetta
Department of Obstetrics and Gynecology, Mauriziano "Umberto I" Hospital, University of Turin, Turin, Italy -
Minerva Ginecol. 2016 Oct;68(5):548-56. Epub 2016 Jan 28.
The surgical option which should be reserved for patients with BRCA1/2 mutation and breast cancer diagnosis is still debated. Several aspects should be considered before the surgical decision-making: the risk of ipsilateral breast recurrence (IBR), the risk of contralateral breast cancer (CBC), the potential survival benefit of prophylactic mastectomy, and the possible risk factors that could either increase or decrease the risk for IBR or CBC. Breast conservative treatment (BCT) does not increase the risk for IBR in BRCA mutation carriers compared to non-carriers in short term follow-up; however, an increased risk for IBR in carriers was observed in studies with long follow-up. In spite of the increased risk for IBR in patients who underwent BCT than patients with mastectomy, no significant difference in breast-cancer specific or overall survival was observed by local treatment type at 15 years. Patients with BRCA mutation had a higher risk for CBC compared with non-carriers and BRCA1-mutation carriers had an increased risk for CBC compared to BRCA2-mutation carriers. Bilateral mastectomy is intended to prevent CBC in BRCA mutation carriers, however, no difference in survival was found if a contralateral prophylactic mastectomy was performed or not. For higher-risk groups of BRCA mutated patients, a more-aggressive surgical approach may be preferable, but there are some aspects that should be considered in the surgical decision-making process. The use of adjuvant chemotherapy and performing oophorectomy are associated with a decreased risk for IBR. When considering the risk for CBC, three risk factors were associated with significantly decreased risk: the use of adjuvant tamoxifen, performing oophorectomy and older age at first breast cancer diagnosis. As a result, we could identify a group of patients that might benefit from a more aggressive surgical approach (unilateral mastectomy or unilateral therapeutic mastectomy with concomitant contralateral prophylactic mastectomy). For women with BRCA mutations candidate to mastectomy, preservation of the nipple-areola complex (NAC) may be highly important due to the generally younger age at time of surgery. Concerning the oncological safety, nipple sparing mastectomy (NSM) is an acceptable option, with no evidence of compromise to oncological safety at short-term follow-up. The evaluation of surgical treatment in breast cancer patients with BRCA 1/2 mutation, should include several issues, namely the current evidence of adequate oncological safety of BCT in BRCA mutated patients; the increased risk for CBC especially in BRCA1 carriers; the feasibility on NSM with a greater patient's satisfaction for cosmetic results with no evidence of compromised oncological safety and, finally, the awareness that breast radiotherapy might increase the risk of complications in a possible subsequent mastectomy with immediate breast reconstruction.
对于携带BRCA1/2突变且已确诊乳腺癌的患者，应选择何种手术方式仍存在争议。在做出手术决策前，应考虑几个方面：同侧乳房复发（IBR）风险、对侧乳腺癌（CBC）风险、预防性乳房切除术的潜在生存获益，以及可能增加或降低IBR或CBC风险的因素。在短期随访中，与非携带者相比，保乳治疗（BCT）并不会增加BRCA突变携带者的IBR风险；然而，在长期随访研究中发现携带者的IBR风险有所增加。尽管接受BCT的患者比接受乳房切除术的患者IBR风险更高，但15年时局部治疗方式在乳腺癌特异性生存或总生存方面并无显著差异。与非携带者相比BRCA突变患者的CBC风险更高，且与BRCA2突变携带者相比，BRCA1突变携带者的CBC风险增加。双侧乳房切除术旨在预防BRCA突变携带者发生CBC，然而，是否进行对侧预防性乳房切除术在生存方面并无差异。对于BRCA突变的高危患者组，更积极的手术方式可能更可取，但在手术决策过程中应考虑一些方面。辅助化疗的使用和进行卵巢切除术与IBR风险降低相关。在考虑CBC风险时，有三个风险因素与风险显著降低相关：辅助他莫昔芬的使用、进行卵巢切除术以及首次诊断乳腺癌时年龄较大。因此，我们可以确定一组可能从更积极的手术方式（单侧乳房切除术或单侧治疗性乳房切除术并同时进行对侧预防性乳房切除术）中获益的患者。对于考虑进行乳房切除术的BRCA突变女性，由于手术时年龄通常较小，保留乳头乳晕复合体（NAC）可能非常重要。关于肿瘤学安全性，保留乳头的乳房切除术（NSM）是一个可接受的选择，短期随访中没有证据表明其会损害肿瘤学安全性。对携带BRCA 1/2突变的乳腺癌患者手术治疗的评估，应包括几个问题，即目前关于BRCA突变患者保乳治疗肿瘤学安全性足够的证据；CBC风险增加，尤其是在BRCA1携带者中；NSM的可行性以及患者对美容效果更高的满意度且没有证据表明肿瘤学安全性受损，最后，要意识到乳房放疗可能会增加后续可能进行的即刻乳房重建乳房切除术的并发症风险。
