Ruth O’Regan

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

The phosphoinositide 3 kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway is a complicated intracellular pathway, which leads to cell growth and tumor proliferation and plays a significant role in endocrine resistance in breast cancer. Multiple compounds targeting this pathway are being evaluated in clinical trials. These agents are generally well tolerated and can be used in combination with targeted therapies, endocrine therapy or cytotoxic agents. The identification of subtypes of tumors more likely to respond to these therapeutics cannot be overemphasized, since breast cancer is a very heterogeneous malignancy. Activation of pathways such as KRAS and MEK can act as escape mechanisms that lead to resistance, thus a combination of agents targeting multiple steps of the intracellular machinery is promising. There is evidence that tumors with PIK3CA mutations are more sensitive to inhibitors of the PI3K pathway but this has yet to be validated. Large clinical trials with correlative studies are necessary to identify reliable biomarkers of efficacy.