Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

Abstract

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed‐up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen‐Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval—CI 18–42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43–2.00), lymphoma (SIR 1.80, 95% CI 1.31–2.40), melanoma (2.12; 1.63–2.70), endometrium (2.18; 1.75–2.70) and kidney cancers (2.40; 1.57–3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post‐menopausal status and a history of full‐term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full‐term pregnancy was inversely associated with the risk of second primary cancer.

Increased risk of colorectal cancer in patients diagnosed with breast cancer in women

“…The SIRs were even higher in premenopausal women (point estimates of SIR were 1.8 and 2.0, but 95%CIs were not reported). In the European Prospective Investigation into Cancer and Nutrition [19], Ricceri et al found an increased risk of colorectal cancer (SIR = 1.71, 95%CI 1.43, 2.00) after diagnosis of breast cancer. In a nested case-control study using SEER data, Kmet et al [37] observed a twofold increase in the risk of colon cancer among breast cancer patients who had either a family history of breast cancer or a high body mass index.…”

“…Several studies have explored the risk of colorectal cancer after a breast cancer diagnosis and treatment, and the results have been inconsistent [15][16][17][18][19][20][21][22].…”

Multiple primary tumours: challenges and approaches, a review

“…21 22 Hormonal treatment of a primary breast cancer increases the risk for endometrial, gastric, colon and ovarian cancers with an excess risk for endometrial cancer observed especially after tamoxifen therapy. 22 Reproductive/hormonal and genetic factors (eg, BRCA1, BRCA2) as well as obesity are recognised as common risk factors for multiple primaries (table 3). 23 For the breast cancer genes BRCA1 and BRCA2, there is a strong association with an increased risk for a second breast or ovarian cancer.…”

“…9 The risk of a second breast, endometrial or ovarian cancer after breast cancer is inversely associated with postmenopausal status and history of full-term pregnancy. 22 Late toxic effects of radiotherapy and chemotherapy also contribute to the increased risk for a secondary primary tumour after breast cancer. Acute myeloid leukaemia (AML) can be induced during the first 2 years after radiotherapy and is a late effect of adjuvant chemotherapy.…”

PEG10 promotes human breast cancer cell proliferation, migration and invasion

“…Breast cancer ranks as the second cause of cancer death among women (1)(2)(3)(4). Clinical cases have indicated that most of the breast cancer deaths are caused by metastasis (5,6), and as a distinct metastatic pattern, breast cancer cells are more inclined to migrate into lymph nodes, bone marrow, lung, liver and brain (7).…”