Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause

Pujol, Pascal; Daurès, Jean‐Pierre; Thézenas, Simon; Guilleux, Fançoise; Rouanet, P.; Grenier, Jean

doi:10.1002/(sici)1097-0142(19980815)83:4<698::aid-cncr10>3.3.co;2-i

Cited by 6 publications

(9 citation statements)

References 17 publications

(27 reference statements)

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“…However, in ER + patients, the clinical therapeutic practices with endocrine therapy to antagonize ER signaling were proven to be 30% effective (65). Hormonal therapy with tamoxifen may only be beneficial for tumors exhibiting nuclear ER expression, since membrane ERs may activate EGFR and/or HER2 signaling, which may then stimulate tumor growth (66) (Fig.…”

Section: Luminal a Subtype Breast Cancer Therapeutic Potentialsmentioning

confidence: 99%

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

et al. 2013

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Abstract. In this review, the advances in the study of breast cancer molecular classifications and the molecular signatures of the luminal subtypes A and B of breast cancer were summarized. Effective clinical outcomes depend mainly on successful preclinical diagnosis and therapeutic decisions. Over the last few years, the ever-expanding investigations focusing on breast cancer diagnosis and the clinical trials have provided accumulating information on the molecular characteristics of breast cancer. Specifically, among the estrogen receptor (ER)-positive types of breast cancer, the luminal subtype A breast cancer has been shown to exhibit good clinical outcomes with endocrine therapy, whereas the luminal subtype B breast cancer represents the more complicated type, diagnostically as well as therapeutically. Furthermore, even in luminal subtype A breast cancer, the resistance to treatment has become the major limitation for endocrine-based therapy. Accumulating molecular data and further clinical trials may enable more accurate diagnostic and therapeutic decisions. The molecular signatures have emerged as a powerful tool for future diagnosis and therapeutic decisions, although currently available data are limited.

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Section: Luminal a Subtype Breast Cancer Therapeutic Potentialsmentioning

confidence: 99%

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

et al. 2013

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“…54 No consistent relationship between plasma estradiol and the ER content of breast carcinomas has been reported. [62][63][64][65] There is a blood-tissue gradient of estradiol that varies considerably between individuals, and, in general, plasma estradiol levels do not reflect tissue estradiol levels.…”

Section: Hormone Receptors and Breast Cancer Proliferationmentioning

confidence: 99%

“…Progesterone, in the presence of a functional PR, can inhibit transcription of the ER gene. 74 The higher progesterone levels in premenopausal women 54 could result in lower ER expression, but only in the presence of PR, which represents less than 50% of the breast carcinomas in premenopausal women. Some peptide hormones, cytokines and growth factors have been shown to alter ER expression 60 and may be present at different levels in pre-and postmenopausal women.…”

Section: Hormone Receptors and Breast Cancer Proliferationmentioning

confidence: 99%

“…The proportion of PR-positive breast carcinomas has been variably reported to be higher in older age groups, 8,[11][12][13]46 lower in postmenopausal women 54 or not varying with age or menopausal status. 16,17 Several studies have found that p27 Kip1 expression does not differ significantly by age or menopausal status.…”

mentioning

confidence: 99%

“…11,46,54 To our knowledge, only 1 prior study has utilized immunohistochemistry to compare breast carcinomas in pre-and postmenopausal women. 59 Our study demonstrated a greater number of ER-positive carcinomas, defined as more than 10% of cells with nuclear staining, in postmenopausal women.…”

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Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

Talley

Grizzle

Waterbor

et al. 2001

Intl Journal of Cancer

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Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile (including negative steroid hormone receptors and a high rate of cellular proliferation) and poor outcome than breast cancers in postmenopausal women. It has been hypothesized that this adverse prognostic profile is a result of the higher histologic grade of breast cancers in pre-compared with post-menopausal women. To assess the association of expression of steroid hormone receptors and indicators of proliferation while controlling for histologic grade, we identified 100 infiltrating ductal carcinomas from premenopausal women 45 years of age or younger and 100 from postmenopausal women 65 years of age or older. The carcinomas were selected so that the histologic grades (low versus high) were distributed equally between the 2 groups. Estrogen receptors (ER), progesterone receptors (PR), p27 Kip1 and Ki-67 (to measure rate of proliferation) were assessed by immunohistochemistry and compared between groups. Clinical information and survival data were also analyzed. ER content was lower and proliferation was higher in carcinomas in premenopausal women (p ‫؍‬ 0.048 and p ‫؍‬ 0.005, respectively). By univariate analysis, p27 Kip1 and PR were not different between the groups; however, in multivariate analysis, p27 Kip1 was higher in postmenopausal women, but only in a subgroup with highly proliferative carcinomas. Overall survival was similar in the pre-and postmenopausal women. Furthermore, low p27 Kip1 and African-American ethnicity predicted a poorer overall survival in the premenopausal, but not in the postmenopausal, women in our study. After controlling for histologic grade, a lower expression of ER and a higher proliferative index were detected in breast carcinomas in premenopausal women. Therefore, some prognostic indicators, such as ER and proliferative rate, may be more closely associated with menopausal status than histologic grade. Our data also suggest that some prognostic factors are not equally effective as predictors of survival in pre-and postmenopausal women. Prognosis in women with breast cancer has been reported to differ according to age and menopausal status. Studies examining this issue have varied in design, age categorization and outcome measures. A few large population-based studies and more limited analyses 1-5 have indicated that women under the ages of 30 -40 years have a worse prognosis. Some retrospective studies have attempted to explain the less favorable outcome in younger women and have reported that breast cancers in younger women exhibit more adverse characteristics, including a high clinical stage at diagnosis, high histologic grade, lack of steroid hormone receptors and increased proliferation. 6 -9 Multivariate analyses to assess associations of age and menopausal status with other clinical and pathologic characteristics have not consistently retained either variable as an independent adverse prognosticator, 8 although several multivariate analyses have indicated that young ag...

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Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance

et al. 2012

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To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element–green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.

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Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause

Abstract: Changes in ER and PgR levels in breast carcinoma during the menstrual cycle and menopause suggest that interpretations of hormone dependency on the basis of steroid receptor values should take into account hormonal status at the time of surgery.

Cited by 6 publications

References 17 publications

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance

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