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Dose of Tamoxifen for Breast Intraepithelial Neoplasia
Patients with breast intraepithelial neoplasia are often treated with tamoxifen to reduce breast cancer risk; however, tamoxifen at the standard dose of 20 mg daily is associated with increased risk for severe adverse events, including endometrial cancer and thromboembolic disease. In preliminary results of a trial of 500 patients with intraepithelial neoplasia, tamoxifen 5 mg daily versus placebo reduced the five-year rate of recurrence or new breast disease (12 versus 6 percent), with similar rates of severe adverse events. However, we continue to recommend tamoxifen 20 mg daily for those with intraepithelial neoplasia, given the preliminary nature of these results and greater clinical trial experience with the 20 mg dose.
Impact of Molecular Subtype on Colorectal Cancer Risk Reduction With Aspirin and NSAIDs
Aspirin and other NSAIDs inhibit colorectal carcinogenesis (CRC), but there are limited data on their CRC risk reduction by molecular subtype. In a population-based case control study, regular use of aspirin or NSAIDs was associated with an approximately 30 percent reduction in CRC risk. Specifically, aspirin or NSAID use was associated with a lower risk of microsatellite stable, BRAF wildtype, and KRAS wildtype CRCs but was not associated with risk reduction for high microsatellite instability, BRAF-mutated, or KRAS-mutated CRCs. Additional studies are needed to validate these results and understand the mechanism through which these agents reduce CRC risk.
Rectum-Sparing Treatment for Early Rectal Cancer
The standard treatment for early (cT1-3N0) rectal cancer is abdominal resection. A prospective study (CARTS) investigated a rectum-sparing protocol of neoadjuvant chemoradiation, followed by transanal local excision in patients with a good clinical response, and then either observation (for ypT0-1) or salvage abdominal resection (for ypT2 or above) depending on pathology. At five years, two-thirds of patients had avoided rectal resection without an adverse effect on oncologic outcome; however, many received unnecessary neoadjuvant radiation and experienced major defecatory symptoms. Therefore, we continue to recommend abdominal resection for early rectal cancer and reserve transanal excision for those who cannot tolerate abdominal surgery.
Combinations of Axitinib and Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma
Both immune checkpoint inhibitors and antiangiogenic therapies (eg, axitinib, sunitinib) have activity in patients with advanced clear cell renal cell carcinoma (CCRCC), and novel combinations continue to be explored in treatment-naïve patients. In separate trials, two different checkpoint inhibitor/antiangiogenic agent combinations (pembrolizumab/axitinib and avelumab/axitinib) improved progression-free survival relative to single-agent sunitinib, while pembrolizumab/axitinib improved overall survival as well. Given these data, we now consider pembrolizumab/axitinib an acceptable frontline treatment for advanced CCRCC, recognizing that comparisons with the existing standard of care, nivolumab and ipilimumab, are lacking, and this remains another reasonable frontline option.
Ovarian Cancer Risk in Women With Polycystic Ovarian Syndrome
Some data suggest that polycystic ovarian syndrome (PCOS) is associated with an increased risk of ovarian cancer, but data are inconclusive. A study based on Swedish registry data for over 14,000 women with PCOS found an approximately twofold increase in ovarian cancer risk. This study contributes additional information regarding PCOS and ovarian cancer risk, but further study is needed. Ovarian cancer risk factors help to guide management of women with an adnexal mass, but current data are insufficient to add PCOS to the list of known risk factors.
Pembrolizumab for Initial Treatment of Metastatic or Recurrent Squamous Head and Neck Cancer
Although the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab is used as a second-line option for metastatic or recurrent squamous cell carcinoma the head and neck, there has been a paucity of data regarding its use as initial therapy. In a preliminary report of the three arm KEYNOTE-048 trial, the addition of pembrolizumab versus cetuximab to frontline platinum and fluorouracil treatment improved overall survival. For those with high PD-L1 expression, single-agent pembrolizumab also improved overall survival compared with cetuximab plus a platinum and fluorouracil combination. These results have been presented in abstract form, and regulatory authorities are evaluating the use of pembrolizumab for this indication. Until approval, the cost of pembrolizumab may limit its use in this patient population.
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