Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor

Abstract

Abstract.Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m 2 (high, H) or <25 kg/m 2 (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR-and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR-tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2-breast cancer in patients treated with adjuvant aromatase inhibitors. IntroductionAromatase inhibitors have been widely administered as adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women. The results of recent clinical trials have demonstrated that third-generation aromatase inhibitors, including anastrozole, letrozole and exemestane, are more effective than tamoxifen in treating early stage or metastatic breast cancer in postmenopausal women (1). Thus, aromatase inhibitors are now considered to be the gold standard of endocrine therapy for such patients in adjuvant and metastatic settings (2,3). Characterization of the risk of recurrence for patients who receive aromatase inhibitors is important for selecting appropriate treatment. However, factors that can predict the outcomes of aromatase inhibitor treatment remain unknown.A number of studies have investigated tumor biomarkers that indicated differential benefit from aromatase inhibitors versus tamoxifen in patients with early breast cancer (4-6). Such biomarkers included the conventional factors, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2) and Ki-67, and did not identify patients who derived a differential relative benefit from aromatase inhibitors over tamoxifen. Expression of the PgR gene is thought to largely depend on an intact ER signaling pathway, and the expression of PgR is associated with endocrine responsiv...

Progesterone receptor status modifies the association between body mass index and prognosis in women diagnosed with estrogen receptor positive breast cancer

“…Interaction** p = 0.15 CI: 1.43-18.00) compared to women with both low BMI (<25 kg/m 2 ) and PR+ tumors. 16 Although their outcome of interest was different from ours, their results are in line with our observations. De Azambuja et al reported poorer overall survival for obese women (BMI > 30 kg/m 2 ) compared to nonobese women (BMI ≤ 30 kg/m 2 ) if the tumor was ER+PR− (HR = 1.91, 95% CI: 1.17-3.12) but not ER+PR+ (HR = 1.13, 95% CI: 0.73-1.75).…”

“…Ohara et al . found that among postmenopausal women with ER+/HER2− tumors and treated with aromatase inhibitor, those with high BMI (≥25 kg/m 2 ) and/or PR− tumors had significantly worst recurrence‐free interval (HR = 5.07, 95% CI: 1.43–18.00) compared to women with both low BMI (<25 kg/m 2 ) and PR+ tumors . Although their outcome of interest was different from ours, their results are in line with our observations.…”

“…A previous study reported that patients with high body mass index (BMI) and/or ER+PR− tumors had worse outcome compared to those with both low BMI and ER+PR+ tumors. 16 This result contrasts with the one from another study concluding that the effect of BMI on outcomes did not differ between ER+PR+, ER+PR−, ER−PR+ and ER−PR− tumors. 17 Given that both BC and obesity are major public health concerns, combined with the lack of studies and conflicting conclusions on the role of PR, more studies are warranted to understand the impact of PR status on the association between BMI and BC prognosis.…”

“…Several studies examined the association between obesity and BC survival by molecular subtypes (luminal A, luminal B, Human epidermal growth factor receptor 2 [HER2] enriched, triple negative), but few directly assessed the impact of PR status. A previous study reported that patients with high body mass index (BMI) and/or ER+PR− tumors had worse outcome compared to those with both low BMI and ER+PR+ tumors . This result contrasts with the one from another study concluding that the effect of BMI on outcomes did not differ between ER+PR+, ER+PR−, ER−PR+ and ER−PR− tumors …”

Optimal body mass index cut‑point for predicting recurrence‑free survival in patients with non‑muscle‑invasive urothelial carcinoma of bladder

“…Indeed, an association between overexpression of insulin receptors in the breast cancer cells of obese patients and poor prognosis has been demonstrated (31). One study has shown that high BMI in conjunction with negative expression of progesterone receptors serves as an independent risk factor for breast cancer recurrences in patients treated with adjuvant aromatase inhibitors (40). In muscle-invasive bladder cancer, expression of insulin receptors in tumor-associated blood vessels also has correlated with poor overall and progression-free survival (41).…”