TY - JOUR
T1 - Effectiveness of Secondary Risk–Reducing Strategies in Patients with Unilateral Breast Cancer with Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery
T2 - Evidence-Based Simulation Study
AU - Maksimenko, Jelena
AU - Rodrigues, Pedro Pereira
AU - Nakazawa-Miklaševiča, Miki
AU - Pinto, David
AU - Miklaševičs, Edvins
AU - Trofimovičs, Genadijs
AU - Gardovskis, Jānis
AU - Cardoso, Fatima
AU - Cardoso, Maria João
N1 - Funding Information:
JM, DP, and MJC conceptualized this study. JM curated the data. PRP performed formal analysis of the study data. JG and FC were responsible for funding acquisition and project administration. JM and PRP proposed the study methodology and wrote the manuscript. MJC, EM, and GT were responsible for acquisition of resources and study supervision. PRP performed software/statistical analysis. JM, PRP, MN-M, MJC, and FC validated the study. JM, MN-M, MJC, EM, and GT performed data visualization. JM, MN-M, MJC, EM, and FC reviewed and edited the manuscript.
Publisher Copyright:
©Jelena Maksimenko, Pedro Pereira Rodrigues, Miki Nakazawa-Miklaševiča, David Pinto, Edvins Miklaševičs, Genadijs Trofimovičs, Jānis Gardovskis, Fatima Cardoso, Maria João Cardoso.
PY - 2022/12
Y1 - 2022/12
N2 - Background: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. Objective: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. Methods: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk–reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Results: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk–reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Conclusions: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.
AB - Background: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. Objective: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. Methods: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk–reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Results: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk–reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Conclusions: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.
KW - BRCA1 and BRCA2
KW - breast cancer
KW - breast-conserving therapy
KW - secondary prophylactic strategies
UR - http://www.scopus.com/inward/record.url?scp=85145616729&partnerID=8YFLogxK
U2 - 10.2196/37144
DO - 10.2196/37144
M3 - Article
AN - SCOPUS:85145616729
SN - 2561-326X
VL - 6
JO - JMIR Formative Research
JF - JMIR Formative Research
IS - 12
M1 - e37144
ER -