Risk of Second Primary Malignancy in Breast Cancer Survivors: A Nested Population-Based Case-Control Study

Abstract

PurposeEvolving therapies have improved the prognoses of patients with breast cancer; and currently, the number of long-term survivors is continuously increasing. However, these patients are at increased risk of developing a second cancer. Thus, late side effects are becoming an important issue. In this study, we aimed to investigate whether patient and tumor characteristics, and treatment type correlate with secondary tumor risk.MethodsThis case-control study included 305 patients with a diagnosed second malignancy after almost 6 months after the diagnosis of primary breast cancer and 1,525 controls (ratio 1:5 of cases to controls) from a population-based cohort of 6,325 women. The control patients were randomly selected from the cohort and matched to the cases according to age at diagnosis, calendar period of diagnosis, disease stage, and time of follow-up.ResultsBRCA1 or BRCA2 mutation, human epidermal growth factor receptor 2 (HER2)+ status, chemotherapy, and radiotherapy were related to increased risk of developing a second cancer, whereas hormonotherapy showed a protective effect. Chemotherapy, radiotherapy, and estrogenic receptor level <10% increased the risk of controlateral breast cancer. HER2+ status increased the risk of digestive system and thyroid tumors, while BRCA1 or BRCA2 mutation increased the risk of cancer in the genital system.ConclusionBreast cancer survivors are exposed to an excess of risk of developing a second primary cancer. The development of excess of malignancies may be related either to patient and tumor characteristics, such as BRCA1 or BRCA2 mutation and HER2+ status, or to treatments factors.

Retrospective Analysis of Patients with Synchronous Primary Breast and Thyroid Carcinoma

“…Although genetic factors, hormones and irradiation have been regarded as risk factors, no absolute relationship has been established yet between them. Either in breast cancer survivors, especially when HER-2 receptor was positive, or in thyroid cancer survivors, increased risk of the other cancer has been found (7,8). This topic has been investigated by cohort and casecontrol studies in survivors butfew studies presented patients diagnosed synchronously and treated at the same time (9,10).…”

Second primary malignancies in cancer survivors: epidemiology, role of anticancer therapy

“…При этом каждая опухоль имеет определенные призна-ки злокачественности, характерные для данной лока-лизации, и не является рецидивом или метастазом предшествующей опухоли в случае вторых и последую-щих первичных опухолей. При рассмотрении этиоло-гии метахронных ПМЗН или вторых первичных опу-холей указываются одни и те же факторы: генетическая обусловленность, экологические условия, факторы обра-за жизни, лучевое и химиотерапевтическое воздействие при лечении первых опухолей [7][8][9][10][11][12][13][14][15]. Национальный институт онкологии США в 1985 г. опубликовал мо-нографию, посвященную первично-множественным опухолям в Коннектикуте и Дании в 1935-1982 гг.…”

“…При наличии синдрома Линча существует высокий риск развития рака толстой и прямой кишки, эндометрия, мочевого пузыря и некоторых других опухолей. Жен-щины с наследственным синдромом РМЖ, который ассоциирован с мутациями в генах BRCA1 и BRCA2, имеют высокий риск и РМЖ и рака яичников, а также некоторых других ЗН [15,21,22].…”

“…Поэтому особого рассмотрения заслуживают отдаленные и наиболее существенные негативные последствия химиотерапии -ее канцеро-генный эффект. Спектр вторых опухолей, развиваю-щихся после химиотерапии, очень широк: это гемо-бластозы и солидные опухоли разных локализаций [15,32,33].…”

Secondary cancer‐incidence risk estimates for external radiotherapy and high‐dose‐rate brachytherapy in cervical cancer: phantom study

“…Although there have been many studies of secondary cancer risk after EBRT, fewer have analyzed secondary cancer risk after brachytherapy (15‐19) . For example, although cervical cancer is usually treated with high‐dose‐rate (HDR) brachytherapy, few studies have analyzed secondary cancer risk due to HDR brachytherapy in patients with cervical cancer.…”