PR, ER expression may predict outcomes in certain ovarian cancers

Issue: September 25, 2013

Expression of estrogen and progesterone receptors was associated with improved survival in women with endometrioid and high-grade serous ovarian cancers, according to study results.

Perspective from Maurie Markman, MD

A global coalition of researchers investigated whether subtype-specific survival was impacted by tumor expression of the progesterone receptor (PR) and estrogen receptor (ER). The Ovarian Tumor Tissue Analysis consortium included clinical and microarray data from 12 studies that included a combined 2,933 women.

Eligible participants included individuals with invasive serous, mucinous, endometrioid or clear-cell carcinoma in the ovaries. The three layers of PR and ER staining included negative (<1% tumor cell nuclei), weak (1 to <50%), or strong (≥50%).

The analysis included 1,742 women with high-grade serous disease, 110 with low-grade serous cancer, 207 with mucinous disease, 484 with cancer of the endometrioid, and 390 with clear-cell disease.

Researchers observed an association between PR expression and increased disease-specific survival among women with endometrial disease (log rank P<.0001) and high-grade serous disease (log rank P=.0006). Researchers also observed an association between ER expression and improved disease-specific survival (log rank P<.0001).

Researchers did not observe significant associations for mucinous, clear-cell or low-grade serious disease.

In comparison with negative expression, all types of positive hormone-receptor expression — including weak and strong ER or PR expression, or both — improved disease-specific survival in endometrial disease. This association persisted across several variables, including age, grade, stage and study site (HR=0.33; 95% CI, 0.21-0.51).

Patients with high-grade serous disease with strong PR expression had improved disease-specific survival (HR=0.71; 0.55-0.91); however, no association was observed in patients with this subtype who had weak PR expression (HR=1.02; 0.89-1.18).

The findings should be beneficial for clinicians with regard to prognosis and hormone therapy among relapsed patients and young disease-free patients who have undergone oophorectomy, Charlie Gourley, MD, PhD, of the Edinburgh Cancer Research UK Centre and Institute of Genetics and Molecular Medicine at the University of Edinburgh Western General Hospital, wrote in an accompanying editorial.

“The role of hormone replacement therapy after oophorectomy at young ages is another controversial and under-researched issue,” he wrote. “By providing a clear picture of the frequency of ER and PR expression in ovarian cancer subtypes, Sieh and colleagues provide a reminder that hormone replacement therapy could affect risk of cancer recurrence, especially in endometrioid carcinoma, low-grade serous carcinoma and high-grade serous carcinoma.”

The findings “imply the identification of important biological subgroups and should promote the reappraisal of endocrine therapy in ovarian cancer,” Gourley added.

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Disclosure: The researchers and Gourley report no relevant financial disclosures.

Perspective

Maurie Markman, MD

The analysis from Sieh and colleagues provides a provocative view of the possible prognostic relevance of hormone receptor expression in specific epithelial ovarian cancer patient subsets. Although it is certainly reasonable to hypothesize that the observed relationship between receptor status (ER/PR expression in endometrioid carcinoma; PR expression in high-grade serous carcinoma) may result from a unique effect of the hormone environment on outcomes, it is equally tenable to speculate that the more favorable prognosis in the setting of receptor expression represents a far more nonspecific relationship where a less malignant cell population may be more likely to continue to reveal “normal” cell surface or intra-cellular markers in contrast to more dedifferentiated cells. Further, such cells would surely be predicted to exhibit a more indolent/favorable biology, even if their morphology could not be distinguished under a light microscope.

One additional point is worthy of comment. In the discussion, the investigators state: “Immunohistochemical analysis of PR and ER expression … could help physicians to counsel patients about their outlook and distinguish between patients who need aggressive chemotherapy and those who might benefit from less toxic endocrine treatment.” Unfortunately, the term “aggressive chemotherapy” is not defined. It must be noted that cytotoxic chemotherapy has a well-established role in ovarian cancer based on the results of multiple phase 3 randomized trials conducted over the past several decades, in striking contrast to essentially the complete lack of such studies regarding hormonal treatment in this malignancy.

Therefore, it is concerning that the authors would make such a strong suggestion based solely on an analysis suggesting the prognostic value of hormone receptor expression in ovarian cancer and in the absence of data that such expression would predict a patient population who would achieve objective clinical benefit from hormonal manipulation. Further, prematurely abandoning the use of known effective cytotoxic agents in ovarian cancer management may quite negatively impact outcome. While the investigators are certainly entitled to their opinions regarding the “aggressiveness” of therapy, it is critical to acknowledge that this philosophy of care should not be confused with a discussion of evidence of clinical benefit.

Maurie Markman, MD

HemOnc Today Editorial Board member

Disclosures: Markman reports no relevant financial disclosures.