Perspective

Prophylactic Mastectomy: A Treatment Alternative for Hodgkin Survivors?

Childhood and young adult survivors of Hodgkin lymphoma are at an elevated risk of developing breast cancer. Breast cancer risk is felt to originate from chest wall radiation exposure prior to the third decade of life, with incidence beginning to rise approximately eight to ten years following Hodgkin lymphoma treatment. Although incidence varies according to age at radiation exposure, dosage, and treatment fields, cohort studies have documented a cumulative incidence of breast cancer of 10–20% by 40 years of age. Women with a history of chest radiation for Hodgkin lymphoma are counselled to begin screening with bilateral breast MRI at 25 years of age, or eight years after radiation, whichever occurs later. Outside of high-risk surveillance, the optimal management approach for women with prior radiation exposure continues to evolve. When diagnosed with breast malignancy, evidence supports consideration of unilateral therapeutic and contralateral prophylactic mastectomy, although breast conserving surgery may be considered following multidisciplinary assessment. This review will address the epidemiology, characteristics, screening and management guidelines, and breast-cancer prevention efforts for Hodgkin lymphoma survivors treated with radiation therapy in adolescence and young adulthood.

Treatment for Hodgkin's lymphoma (HL) has evolved, with modern treatments combining less toxic chemotherapy and radiation, leading to improved long-term disease-free survival. However, there is a higher chance of second cancer, especially breast cancer, following effective HL treatment. The impact of reduced radiation doses and volumes, as well as the use of advanced irradiation techniques, on the risk of second malignancy is not clear. According to medical organizations, the history of chest irradiation is a relative contraindication to breast preservation therapy for women with initial breast cancer, leading to a paradigm of mastectomy. This article proposes a discussion between radiation oncologists and surgeons to review major trials and recent developments on the prevalence of breast cancer following HL therapy, the risk of contralateral cancer, the feasibility of breast conserving surgery (BCS), as well as breast reconstruction modalities.

Breast cancer is associated with a multitude of risk factors, such as genetic predisposition and mutations, family history, personal medical history, or previous radiotherapy. A prophylactic mastectomy (PM) may be considered a suitable risk-reducing procedure in some cases. However, there are significant discrepancies between national society recommendations and insurance company requirements for PM.

The authors conducted a cross-sectional analysis of insurance policies for a PM. One-hundred companies were selected based on the greatest state enrolment and market share. Their policies were identified through a Web-based search and telephone interviews, and their medical necessity criteria were extracted.

Preauthorized coverage of PMs was provided by 39% of insurance policies (n = 39) and 5 indications were identified. There was consensus amongst these policies to cover a PM for BRCA1/2 mutations (n = 39, 100%), but was more variable for other genetic mutations (15%-90%). Coverage of PM for the remaining indications varied among insurers: previous radiotherapy (92%), pathological changes in the breast (3%-92%), personal history of cancer (64%) and family history risk factors (39%-51%).

There is a marked level of variability in both the indications and medical necessity criteria for PM insurance policies. The decision to undergo a PM must be carefully considered with a patient's care team and should not be affected by insurance coverage status.

Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers’ care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.

The risk of women developing a breast cancer (BC) after receiving chest radiotherapy for paediatric cancers and Hodgkin lymphomas is well established. The aim of this study was to assess these patients’ clinical characteristics and clinical outcomes.

The study concerns women with a history of primary neoplasms treated with chest irradiation ± chemotherapy and subsequently diagnosed with BC.

We identified 78 women who developed BC (invasive in 68 cases, 87%). They were a median 18 and 38 years of age when their first neoplasm and BC were diagnosed, respectively. Breast-conserving surgery was performed in 39 patients, and 32 underwent breast irradiation. Twenty of the 41 patients (49%) treated with chemotherapy received an anthracycline-containing regimen.

The 5- and 11-year event free survival (EFS) and overall survival (OS) rates were 69% and 42%, respectively. Nine patients (12%) developed a third cancer and 18 (23%) a cardiovascular event. Of the 68 women with invasive BC, the first event involved contralateral BC in 55% of cases: time to progression (TTP) rates were 70% and 47% at 5 and 11 years. The 5- and 11-year BC-specific survival rates (BCSS) were 84% and 68%, respectively.

Judging from our experience, survival rates after BC developing in women previously given chest radiotherapy are not dissimilar to those observed in other women with primary BC. Given the far from negligible risk of subsequent cancers and cardiovascular events, it is mandatory to discuss the best choice of treatment for such patients in terms of their chances of cure and quality of life, and also the risks of late sequelae.