CBCRisk model to determine the risk of contralateral breast cancer in sporadic breast cancer

Abstract

Introduction

The great majority of breast cancer (BC) cases are diagnosed in women who have no known family history of the disease and are not carriers of any risk mutation. During the past few decades an increase in the number of contralateral prophylactic mastectomy (CPM) has been produced in these patients. The CBCRisk model calculates the absolute risk of suffering from contralateral breast cancer (CBC); thus, it can be used to counselling patients with sporadic breast cancer.

Method

An observational, retrospective study including sporadic breast cancer patients treated with contralateral prophylactic mastectomy has been conducted between 2017 and 2019. A descriptive and comparative study with one variation of logistic regression has been carried out in order to identify predictive factors of occult tumors (OT) and medium/high risk damage (MHRD). Evaluation of the CBCRisk model published in 2017 and different limit values for the CPM recommendation.

Results

42 patients were selected. Incidence of MHRD and OT was lower than that described in the literatura (9.52%MHRD, 2.38%OT). None of the evaluated variables reached statistical significance for predicting injuries. The average value of CBCRisk 5 years ahead found in patients with pathological findings was 2.08 (DE 0.97), higher than the average value of the whole group (1.87 ± 0.91) and the subgroup without pathological findings (1.84 ± 0.91). Only values >3 for CBCRisk were considered statistically significant (P = .04) for the prediction of histological lesions.

Conclusion

Patients with sporadic breast cancer should be adequately informed about the estimated risks and benefits of undergoing a contralateral prophylactic mastectomy. The CBCRisk may be useful for the counseling of these patients, but it requires validation in larger and prospective cohorts.

Resumen

Introducción

La mayoría de los cánceres de mama (CM) se diagnostican en mujeres sin antecedentes familiares y no portadoras de mutaciones de riesgo. En las últimas décadas se ha producido un aumento de mastectomías profilácticas contralaterales (MPC) en estas pacientes. El CBCRisk es un modelo que calcula el riesgo absoluto de cáncer de mama contralateral (CMC) y pretende servir para el asesoramiento de pacientes con CM esporádico sobre la MPC.

Método

Análisis observacional retrospectivo de pacientes con un cáncer de mama esporádico sometidas a MPC durante 2017−2019. Análisis descriptivo, comparativo y de regresión logística univariante para identificar factores predictivos de LMAR y/o CMC oculto. Evaluación del modelo CBCRisk publicado en 2017 y distintos valores límite para la recomendación de MPC.

Resultados

Se seleccionaron 42 pacientes. Incidencia de LMAR y CO menor que la descrita en la literatura (9.52%LMAR, 2,38%CO). Ninguna de las variables evaluadas alcanzó significación estadística para la predicción de lesiones. El valor de CBCRisk a 5 años medio en pacientes con hallazgos patológicos fue de 2.08(DE 0.97), superior al CBCRisk medio del conjunto (1.87 ± 0.91) y del subgrupo de MPC sin hallazgos patológicos (1.84 ± 0.91). Sólo el CBCRisk>3 resultó significativo (P = .04) para la predicción de hallazgos patológicos.

Conclusión

Las pacientes con CM esporádico deben ser adecuadamente informadas de los riesgos y beneficios estimados de la MPC. El CBCRisk puede ser útil para el asesoramiento de estas pacientes, pero precisa validación en cohortes más amplias y prospectivas.

Introduction

Contralateral prophylactic mastectomy (CPM) has been evaluated as a strategy for reducing the risk of contralateral breast cancer (CBC) in patients with sporadic breast cancer (BC) (ie, no mutations in the main genes associated with hereditary breast cancer, and no strong family history)¹.

CPM is the therapeutic strategy that provides the greatest reduction in the risk of CBC. It reduces the need for follow-up controls along with the concern and anxiety of patients, while providing benefits in terms of symmetrization. However, it is a compromising procedure: it is aggressive and irreversible; it doubles the risk of surgical complications²; it can delay the administration of adjuvant therapies; it often requires other procedures (mainly due to the association of some type of breast reconstruction); it can be associated with chronic pain³ and may negatively influence the mental and sexual health of patients⁴. Furthermore, the benefits of CPM in terms of survival of women who are not carriers of BRCA mutations has not been clearly demonstrated, except perhaps for women under the age of 49 with triple negative tumors⁵.

Consensus indications¹ for CPM include a history of supradiaphragmatic radiation before the age of 30 and a demonstrated BRCA 1/2 mutation. It can be considered in the case of CHEK2/PTEN/p53/PALB2/CDH1 mutation carriers, patients with a strong family history without demonstrated risk mutations, or in the case of significant asymmetry after unilateral mastectomy (with or without reconstruction).

In recent decades, we have witnessed an increase in the performance of CPM in patients with sporadic BC, more notable among the US population than in the European population due to social and cultural factors that have not yet been clarified6, 7. This fact is paradoxical as the early diagnosis of BC together with improved adjuvant therapies has meant that, on the one hand, the possibilities of breast-conserving techniques has increased (expanded indications for breast-conserving surgery), while the recurrence, mortality and incidence of CBC have decreased⁸.

Some authors attribute this increase in CPM to patients overestimating the risk of CBC, as well as the generalized access to immediate reconstruction1, 6.

Until the publication of the absolute risk predictive model (CBCRisk⁹) in 2017, there was no useful quantitative tool for individual CBC risk assessment in women with sporadic unilateral BC. This model calculates the absolute risk of CBC by periods, through the combination of eight risk factors: age at diagnosis of the first BC, antiestrogenic therapy, first-degree family history of BC, previous moderate/high-risk lesions (MHRL), estrogen receptor status, breast density at diagnosis, type of primary tumor, and age at birth of the first child. The tool is specially designed for women with sporadic unilateral BC, as it does not include information on risk of mutations.

Subsequently, the ability of the model to discriminate between women with high/low risk of CBC was evaluated in two independent cohorts¹⁰, but the follow-up data only allowed this to be done for a period of three to five years. The authors concluded that, although there are differences depending on the prevalence of BC, the characteristics of the cohort and the parameters coded as “unknown”, the model can be useful for individual counseling in routine clinical practice.

The objective of this study is to evaluate whether the CBCRisk is able to identify patients with a greater probability of presenting MHRL or occult malignancy in the contralateral breast, thereby making it possible to identify patients who would obtain the greatest benefit from CPM.