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Updated guidelines on estrogen and progesterone receptor testing in breast cancer
The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) has again established the threshold for a positive result for hormone receptor expression in breast cancer as at least 1 percent of cancer cells staining for estrogen receptor (ER) or progesterone receptor (PR) [1]. New to this guideline, however, is a recommendation for a new category, "ER Low Positive," for cancers with 1 to 10 percent of cells staining for ER, reflecting the limited data supporting efficacy of endocrine therapy in this population. Practically, this means that all patients with breast cancers that have ER or PR expression of at least 1 percent should be offered endocrine therapy. However, if patients with breast cancer ER expression of 1 to 10 percent do not tolerate treatment for whatever reason, it may be reasonable to discontinue therapy. By contrast, patients whose breast cancers demonstrate greater than 10 percent staining should be urged to continue endocrine therapy, if at all possible, due to strong evidence of beneficial effects.
Maintenance olaparib for BRCA-mutated advanced pancreatic cancer
Up to 7 percent of pancreatic cancers lack BRCA1 or BRCA2 activity because of a mutation in the BRCA or PALB2 genes; deficiency in the repair of DNA double-strand breaks makes them more sensitive to platinum agents and to poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors. In the randomized POLO trial, which included 154 patients with germline BRCA-mutated metastatic pancreatic cancer that had not progressed during at least 16 weeks of first-line platinum-based chemotherapy, olaparib improved progression-free survival relative to placebo [2]. Over twice as many patients assigned to olaparib were still progression-free at two years (22 versus 10 percent). Based on these results, olaparib was approved by the US Food and Drug Administration in December 2019 for first-line maintenance therapy of patients with BRCA gene mutations whose cancer has spread beyond the pancreas, and whose tumors did not worsen after chemotherapy of at least 16 weeks [3]. We suggest olaparib as maintenance therapy for patients with advanced, BRCA or PALB2 germline-mutated pancreatic cancer who do not experience progression after at least 16 weeks of initial platinum-containing therapy.
Lower dose of olanzapine for cisplatin-related nausea
The addition of the second-generation antipsychotic olanzapine (10 mg daily on days 1 to 4) to conventional antiemetics improves control of both acute and delayed chemotherapy-induced nausea and vomiting (CINV) from highly emetogenic chemotherapy, although it also increases daytime somnolence. The placebo-controlled J-Force trial demonstrated clinically significant improvements in complete control of CINV in both the acute and delayed phases with a smaller 5 mg daily dose of olanzapine added to conventional antiemetics in patients receiving cisplatin-based highly emetogenic chemotherapy, without worse daytime somnolence [4]. Based upon these data, olanzapine 5 mg is preferred over the 10 mg dose in the setting of cisplatin-based highly emetogenic chemotherapy, but for patients receiving an anthracycline plus cyclophosphamide, there are insufficient data to recommend the lower dose for prevention of CINV.
hCG surveillance after molar pregnancy
In patients with a complete mole who achieve human chorionic gonadotropin(hCG) normalization during postevacuation monitoring, the International Federation of Gynecology and Obstetrics (FIGO) recommends six additional months of hCG monitoring for confirmation. However, in a meta-analysis evaluating the frequency of gestational trophoblastic neoplasia (GTN) after initial normalization, the risk of GTN was very low (0.35 percent after a complete mole and 0.03 percent after a partial mole) and few cases occurred within the six-month confirmatory monitoring period [5]. For patients with partial moles, we obtain a confirmatory hCG level one month after normalization; for those with complete moles, these data support our approach of decreasing monitoring from six to three months postnormalization, although we recognize that even shorter surveillance periods may also be appropriate [6].
1. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol 2020; :JCO1902309.
2. Golan T, Hammel P, Reni M, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med 2019; 381:317.
3. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/208558Orig1s010ltr (Accessed on January 02, 2020).
4. Hashimoto H, Abe M, Tokuyama O, et al. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019.
5. Albright BB, Shorter JM, Mastroyannis SA, et al. Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy: A Systematic Review and Meta-analysis. Obstet Gynecol 2020; 135:12.
6. Horowitz NS, Berkowitz RS, Elias KM. Considering Changes in the Recommended Human Chorionic Gonadotropin Monitoring After Molar Evacuation. Obstet Gynecol 2020; 135:9.
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