Herediter Meme Kanserinde Cerrahi Yaklaşım
Özet
Meme kanseri, yıllık 2,3 milyon yeni olguyla dünya genelinde en sık görülen kanser türü haline gelmiştir. Hastalık vakalarının %70-80'i sporadik, %15-20'si ailesel ve %5-10'u ise genetik geçişli herediter meme kanseri (HMK) olarak sınıflandırılmaktadır. HMK; erken yaşta ortaya çıkması, bilateral görülme eğilimi ve otozomal dominant kalıtım paterniyle ayırt edilir. Kalıtsal olguların %50-60'ından BRCA1 ve BRCA2 gen mutasyonları sorumludur. Bu mutasyonları taşıyan kadınlarda yaşam boyu meme kanseri gelişme riski %87'ye kadar çıkabilmektedir. Ayrıca TP53, PTEN, CDH1, PALB2, CHEK2 ve ATM gibi yüksek ve orta penetranslı diğer gen mutasyonları da meme ve ilişkili ek kanserlerin riskini anlamlı ölçüde artırmaktadır. HMK şüphesi veya tanısı olan bireylerde yönetim; kişiselleştirilmiş erken tarama protokollerini (mamografi ve özellikle gençlerde duyarlılığı yüksek olan MRG) ve risk azaltıcı stratejileri kapsamaktadır. Asemptomatik mutasyon taşıyıcılarında bilateral profilaktik mastektomi, meme kanseri riskini %93'e varan oranda azaltmaktadır. Terapötik yaklaşımda ise mutasyon tipine göre meme koruyucu cerrahi veya radyoterapi kontrendikasyonları (örneğin TP53 mutasyonunda) dikkate alınarak kontralateral profilaktik mastektomi seçenekleri multidisipliner bir yaklaşımla değerlendirilmelidir.
Breast cancer has become the most frequently diagnosed cancer worldwide, with approximately 2.3 million new cases annually. While 70-80% of cases are sporadic and 15-20% are familial, about 5-10% are classified as hereditary breast cancer (HBC), which is characterized by an early age of onset, bilateral occurrence, and an autosomal dominant inheritance pattern. Pathogenic germline mutations in the BRCA1 and BRCA2 genes account for 50-60% of all hereditary cases, elevating the lifetime breast cancer risk up to 87%. Additionally, other high- and moderate-penetrance genes such as TP53, PTEN, CDH1, PALB2, CHEK2, and ATM significantly increase the risks of breast and associated syndromic malignancies. Management of individuals with suspected or confirmed HBC involves personalized early surveillance protocols—utilizing mammography and breast MRI, which offers superior sensitivity in young dense breasts—alongside risk-reducing strategies. In asymptomatic mutation carriers, bilateral prophylactic mastectomy can reduce the risk of developing breast cancer by up to 93%. For therapeutic surgical management, options including breast-conserving surgery or contralateral prophylactic mastectomy must be evaluated through a multidisciplinary approach, carefully considering mutation-specific contraindications to radiation therapy, such as those found in TP53 carriers.
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