Accepted for/Published in: JMIR Formative Research
Date Submitted: Feb 18, 2022
Date Accepted: Nov 1, 2022
Effectiveness of secondary risk-reducing strategies in unilateral breast cancer patients with pathogenic variants of BRCA1 and BRCA2 subjected to breast-conserving surgery: an evidence-based simulation study.
ABSTRACT
Background:
Approximately 62% of patients with BRCA1/2– related breast cancers underwent a primary breast-conserving therapy. The aim of the present study was to develop a personalized risk management guideline for BRCA1/2 carriers who underwent breast-conserving therapy for unilateral early stage breast cancer.
Objective:
The aim of the present study was to develop a personalized decision support tool for BRCA1/2 carriers who underwent BCT for unilateral early stage breast cancer.
Methods:
We have developed a Bayesian network model of a hypothetical cohort of BRCA1/2 carriers diagnosed with stage I-II unilateral breast cancer and treated with BCT who underwent the subsequent second primary cancer prevention strategies. We predicted the 40 -year overall survival of different prevention strategies for 144 cohorts of women defined by the type of BRCA1/2, age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, presence or absence of adjuvant chemotherapy.
Results:
Absence of adjuvant chemotherapy was the most powerful factor that was linked to dramatic decline in survival for BRCA1/2 breast cancer patients. Most BRCA1/2 carriers with luminal breast cancer, profited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. There was a negligible decline in the mortality in BRCA1/2 carriers with triple-negative breast cancer, who received no chemotherapy and underwent any secondary prevention strategy compared to surveillance. The potential survival benefit from any preventive strategy was more modest in triple-negative breast cancer patients, who received chemotherapy compared to luminal breast cancer patients. There were patients with triple-negative and luminal breast cancer, who gained a similar survival benefit from risk-reducing bilateral mastectomy or risk-reducing salpingoohorectomy or surveillance.
Conclusions:
Our study showed, that most BRCA1/2 carriers with stage I-II unilateral breast cancer, who were treated with breast- conserving therapy profited from bilateral risk-reducing mastectomy and risk- reducing salpingo-oophorectomy. However, BRCA1/2 carriers with triple-negative breast cancer, who received no chemotherapy and most of older patients with BRCA1/2 pathogenic variants in exon 12-24/25 with luminal breast cancer may gain a similar survival benefit from other prophylactic strategies or surveillance.
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