Steroid hormone receptors and carcinoma of the breast

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50-60% are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of subsequent relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of ER and assay of progesterone receptor (PgR) are useful for increasing the accuracy of selecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be the best available tumor marker of hormone dependence.

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New therapeutic opportunities for low-grade serous ovarian cancer

Endocrine Related Cancer ◽

10.1530/erc-21-0191 ◽

2021 ◽

Author(s):

Tania Moujaber ◽

Rosemary L Balleine ◽

Bo Gao ◽

Ida Madsen ◽

Paul R Harnett ◽

...

Keyword(s):

Ovarian Cancer ◽

Hormone Receptors ◽

Residual Disease ◽

Objective Response ◽

Response Rates ◽

Steroid Hormone Receptors ◽

Mitogen Activated Protein Kinase ◽

Low Grade ◽

Serous Ovarian Cancer ◽

Platinum Based Chemotherapy

Low-grade serous ovarian cancer (LGSC) is a morphologically and molecularly distinct subtype of ovarian cancer, accounting for ~10% of serous carcinomas. Women typically present at a younger age and have a protracted clinical course compared with the more common, high-grade serous ovarian cancer. Currently, primary treatment of LGSC is the same as other epithelial ovarian cancer subtypes, with treatment for most patients comprised of debulking surgery and platinum/taxane chemotherapy. Primary surgical cytoreduction to no visible residual disease remains a key prognostic factor, however the use of platinum-based chemotherapy in both the upfront and relapsed setting, is being questioned due to low response rates in LGSC. Most LGSC express steroid hormone receptors and selected patients may benefit from endocrine maintenance therapy following chemotherapy, in particular those with evidence of residual disease at completion of surgery. In the recurrent setting, while hormonal therapies may offer disease stabilization with relatively low toxicity, objective response rates remain low. Strategies to increase response rates, including combining with CDK4/6 inhibitors, are being investigated. LGSC have a high prevalence of activating somatic mutations in mitogen-activated protein kinase pathway genes, most commonly in KRAS, BRAF and NRAS. Trametinib, a MEK inhibitor, has shown efficacy over chemotherapy and endocrine therapy. The use of combination targeted therapies, immunotherapy and anti-angiogenic agents, remain active areas of investigation for the treatment of LGSC.

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