Panorama of diseases associated with breast cancer

Abstract

Breast cancer is the most common cancer in women. Although the incidence of breast cancer has increased over time, so too has patient survival. Given these trends, the prevalence of breast cancer has steadily increased in recent decades, exposing these women to other associated diseases which can influence carcinogenesis, prognosis, and treatment. This thesis uses Swedish register data, combined with data from the Libro-1 and Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohorts, to study other diseases associated with breast cancer in women. Specifically, this thesis investigates how diseases in early adulthood influence the risk of breast cancer, and how overall health is affected by breast cancer treatment.

In Study I, the risk of breast cancer in women with and without preeclampsia was studied using data from the Swedish Medical Birth Register and KARMA cohort. Women diagnosed with preeclampsia had a decreased risk of breast cancer and lower mammographic density. In addition, sisters of breast cancer patients and women with a high genetic predisposition to breast cancer had a lower risk of preeclampsia. This suggests that inherited factors may contribute to the inverse association between preeclampsia and breast cancer. In Study II and Study III, the risk of mental disorders and psoriasis were compared between a Swedish nationwide cohort of breast cancer patients and the general population. Women with invasive breast cancer had an increased risk of depression, anxiety, stress-related disorders, and psoriasis. This increased risk was greatest shortly after cancer diagnosis and remained over the subsequent five years. Patients with in-situ breast cancer only experienced an increased risk of stress-related disorders during the first six months after cancer diagnosis. With regard to risk predictors, the Libro-1 cohort of Stockholm-Gotland breast cancer patients showed that younger age at diagnosis, higher tumor grade, lymph node positive tumors, comorbidity, and chemotherapy were independently associated with an increased risk of depression and anxiety. The effect of tumor grade and chemotherapy was mainly limited to the first two years after diagnosis, while comorbidity contributed to long term risk. Younger age at diagnosis was the only risk factor identified for stress-related disorders; while for psoriasis, radiotherapy and mastectomy were associated with increased disease risk. Aside from these treatment-specific predictors, genetic predisposition, obesity and smoking were also risk factors for psoriasis in breast cancer patients. Study IV used a matched cohort design to describe a wide spectrum of diseases after breast cancer diagnosis. In a Swedish nationwide breast cancer cohort, breast cancer patients had an increased risk of infection and several non-communicable diseases, compared to matched healthy individuals. Diseases with the highest hazard ratios - lymphedema, radiodermatitis, and neutropenia - correspond to the side effects of surgery, radiotherapy, and chemotherapy. Despite an increased incidence of many diseases, increased mortality risk among breast cancer patients was only due to other solid cancers. A higher risk of other solid cancers could be predicted by menopausal disorders, indicating the need for gynecological surveillance of breast cancer patients.

In conclusion, our results suggest that inherited factors contribute to an inverse association between preeclampsia and breast cancer, given that the inverse association was also found between preeclampsia and women with a high genetic predisposition to breast cancer. This thesis identifies an increased risk of several diseases after breast cancer diagnosis, including menopausal disorders, mental disorders, and psoriasis. Such diseases are related to cancer treatment, and suggest that a multidisciplinary perspective on post-cancer care is required for breast cancer patients.