Atypical hyperplasia of the breast: Clinical cases and management strategies.

Atypical hyperplasia of the breast is a histopathologic lesion identified incidentally on image-guided breast biopsy. It is associated with a substantial increase in lifetime risk for breast cancer. Clinicians should counsel women with atypical hyperplasia regarding risk-reducing strategies, which include preventive endocrine therapy options, enhanced surveillance imaging, and lifestyle modifications. In this review, we describe 5 different but common clinical case scenarios for atypical hyperplasia of the breast and review management strategies for each scenario.

Association Between Lifestyle Changes, Mammographic Breast Density, and Breast Cancer.

In screening for breast cancer (BC), mammographic breast density (MBD) is a powerful risk factor that increases breast carcinogenesis and synergistically reduces the sensitivity of mammography. It also reduces specificity of lesion identification, leading to recalls, additional testing, and delayed and later-stage diagnoses, which result in increased health care costs. These findings provide the foundation for dense breast notification laws and lead to the increase in patient and provider interest in MBD. However, unlike other risk factors for BC, MBD is dynamic through a woman's lifetime and is modifiable. Although MBD is known to change as a result of factors such as reproductive history and hormonal status, few conclusions have been reached for lifestyle factors such as alcohol, diet, physical activity, smoking, body mass index (BMI), and some commonly used medications. Our review examines the emerging evidence for the association of modifiable factors on MBD and the influence of MBD on BC risk. There are clear associations between alcohol use and menopausal hormone therapy and increased MBD. Physical activity and the Mediterranean diet lower the risk of BC without significant effect on MBD. Although high BMI and smoking are known risk factors for BC, they have been found to decrease MBD. The influence of several other factors, including caffeine intake, nonhormonal medications, and vitamins, on MBD is unclear. We recommend counseling patients on these modifiable risk factors and using this knowledge to help with informed decision making for tailored BC prevention strategies.

Local Recurrence of Invasive Secretory Breast Carcinoma in a Gravid Patient Post-Mastectomy.

This is a case of locally recurrent invasive secretory carcinoma of the breast during pregnancy, detected as a palpable mass in the reconstructed right breast of a 32-year-old female at 24 weeks gestation. The patient was initially diagnosed with secretory carcinoma 8 years prior, for which she underwent nipple sparing mastectomy followed by adjuvant chemotherapy and endocrine therapy. Due to pregnancy, the recurrence was treated initially with conservative excision alone, followed by definitive management postpartum which included wide local excision, sentinel lymph node biopsy and adjuvant chest wall radiation. Secretory carcinoma of the breast is a rare cancer with a predilection for young age and indolent course. This case report describes an unusual case of recurrent secretory carcinoma, of interest due to both its diagnosis during pregnancy, and its recurrence after nipple sparing mastectomy.

Identifying women with increased risk of breast cancer and implementing risk-reducing strategies and supplemental imaging.

Breast cancer (BC) is the second most common cancer in women, affecting 1 in 8 women in the United States (12.5%) in their lifetime. However, some women have a higher lifetime risk of BC because of genetic and lifestyle factors, mammographic breast density, and reproductive and hormonal factors. Because BC risk is variable, screening and prevention strategies should be individualized after considering patient-specific risk factors. Thus, health care professionals need to be able to assess risk profiles, identify high-risk women, and individualize screening and prevention strategies through a shared decision-making process. In this article, we review the risk factors for BC, risk-assessment models that identify high-risk patients, and preventive medications and lifestyle modifications that may decrease risk. We also discuss the benefits and limitations of various supplemental screening methods.

Simultaneous inhibition of focal adhesion kinase and SRC enhances detachment and apoptosis in colon cancer cell lines.

Focal adhesion kinase (FAK) and Src have been shown to be overexpressed in colon cancer. We have studied the role of these two kinases in resistance to apoptosis. Adenovirus-containing FAK-CD (Ad-FAK-CD), a dominant-negative, COOH-terminal portion of FAK, was used to inhibit FAK and cause apoptosis. Colon cancer cell lines were more resistant to Ad-FAK-CD-induced detachment and apoptosis than the breast cancer cell line, BT474. Colon cancer cell lines overexpressed highly active Src and FAK. Ad-FAK-CD-induced apoptosis was significantly increased by PP2, an inhibitor of Src family kinases. Activation of caspase-3, down-regulation of FAK, and Src and AKT activities were demonstrated in Ad-FAK-CD + PP2-treated colon cancer cells undergoing apoptosis. The results suggest that FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Ad-FAK-CD-induced apoptosis. Dual inhibition of these kinases may be important for therapies designed to enhance the apoptosis in colon cancers.