Triple-negative Breast cancer (sometimes abbreviated TNBC, 삼중음성 유방암) refers to any breast cancer that does not express the genes for Estrogen receptor (ER), Progesterone receptor (PR) or HER2. (https://en.wikipedia.org/wiki/Triple-negative_breast_cancer)

Introduction #

매우 다양한 서브타입을 모두 포함한다. 일부는 예후가 좋지만, 일부는 그렇지 않다. 약 75%의 basal-type 유방암이 삼중음성 유방암이다. basal은 luminal에 비해 덜 분화된 상태를 의미한다. 일부 TNBC는 EGFR을 과발현하며, 또 일부는 GPNMB를 과발현한다.

젋은 여성에게, 그리고, African ancestry 여성에게, 그리고, BRCA1, BRCA2 변이 여성에게 많이 발견된다. 또한 젋은 여성의 TNBC는 경구용 피임약과도 관련있다는 보고가 있다.

Ethnicity #

미국내에서 African은 Caucacian 보다 2배 많다. Ashkenazi 유대인종은 10배 더 많음.

Treatments #

Local therapy (surgery and radiation)

• Breast-conserving surgery (lumpectomy)
• Bilateral mastectomy (BRCA 변이가 있을 때)

Systemic therapy (medications)

• Anthracycline-based regimens (course of treatment)
  • AC [doxorubicin, cyclophosphamide] followed by T [docetaxel]
  • TAC [docetaxel, doxorubicin, cyclophosphamide]
• Nonanthracycline regimens
  • TC [docetaxel, cyclophosphamide]

When Metastatic TNBC

• Standard chemotherapy
• Platinum therapy: Cisplatin, Carboplatin
• PARP inhibitor: Olaparib, Iniparib
• Less promising study results
  • Angiogenesis inhibitors: Bevacizumab + Paclitaxel
  • RTK inhibitors: Sorafenib, Sunitinib

Potential new therapy

• EGFR inhibitors (50% 이상의 TNBC에서 발현): Cetuximab + Cisplatin
• PI3K inhibitors

관련 자료 #

기사 #

• 삼중음성유방암, 아바스틴 급여돼야 의협신문 2015-11-30
• 기존 치료법 내성 관여하는 암 유전자 발견… 난치성 ‘삼중음성 유방암’ 치료 새 길 열어 경향신문 2015-03-31: MEL-18의 소실이 여성호르몬 수용체를 감소시켜 삼중음성 유방암과 치료에 대한 내성을 유발함. 동물실험에서 TNBC에 MEL-18 증가시키는 방식으로 항호르몬 약제 Tamoxifen 효과 56% 상승
• 삼중음성유방암, 표적치료 가능하나 문제는 비용 청년의사 2015-03-01: VEGF 표적 Bevacizumab (아바스틴) 보험돼야.
• 삼중음성유방암 원인 유전자 찾았다 헬스코리아뉴스 2015-01-13: TNBC 3000명 분석하여 BCL11A 변이 발견 - 수년 내 재발 가능성도 높음
• 빅데이터 의학, 암을 정복할까 동아사이언스 2013-05-03: 항암제와 그 반응성과의 Data analysis를 통해 TNBC의 치료 방법 제안 - DNA repair 관련 약물을 일정시간 투입한 후, 성장 호르몬 수용체 조절 약물(EGFR로 추정?)을 투입했더니 현저히 사멸 - 실제 실험결과도 그러함. Cell에 실림

웹사이트 #

• Triple Negative Breast Cancer Foundation

논문 #

TNBC 일반 #

• Triple-negative breast cancer: an unmet medical need The Oncologist 2011

서브타입 구분 #

• Biomarkers in triple negative breast cancer: A review World Journal of Clinical Oncology 2015-12-10
• Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype Oncotarget 2015-05-07: TNBC는 비균일한 구분체계임. 이를 다시 5개 subtype으로 구분함 (basal-like, mesenchymal-like, immune-associated, luminal/apocrine, HER2-enriched)
• Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists Modern Pathology 2010-11-12: basal-like와 TNBC의 구분

관련 유전자 #

• BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells Nature Communications 2015-01-09: BCL11A 중요
• Meta-analysis of the global gene expression profile of triple-negative breast cancer identifies genes for the prognostication and treatment of aggressive breast cancer Oncogenesis 2014-03-10: Meta-analysis로 TTK 등 발견

NGS 관련 #

• Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study Nature Medicine 2019-09-30: Serena Nik-Zainal 논문. 254 TNBC 사례를 WGS 하고, 예후 예측 모델을 만듬.
• Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology Modern Pathology 2016-03-04
• Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response Breast Cancer Research 2015-10-03

치료 타겟 #

• Dual PI3K and Wnt pathway inhibition is a synergistic combination against triple negative breast cancer Nature 2017-04-26: PI3K와 Wnt signaling pathway를 조합할 때 시너지 효과 있음

Incoming Links #

[Medical Scholarly Articles] About (MedicalScholarlyArticle 0) #

• Biomarkers in triple negative breast cancer: A review
• Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology
• Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype
• Meta-analysis of the global gene expression profile of triple-negative breast cancer identifies genes for the prognostication and treatment of aggressive breast cancer
• Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response
• Triple-negative breast cancer: an unmet medical need

Related Medical Scholarly Articles (MedicalScholarlyArticle 1) #

• BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells
• CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer
• Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology
• Landscape of somatic mutations in 560 breast cancer whole-genome sequences
• Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response

Related Articles (Article 2) #

• Copy-number variation

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