Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study

Purdie, Colin A.; Quinlan, P; Jordan, Lee B.; Ashfield, A.; Ogston, Simon; Dewar, John; Thompson, Alastair

doi:10.1038/bjc.2013.756

Cited by 150 publications

(142 citation statements)

References 42 publications

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“…The difference in HR may be due to biological differences between ER and PR. Strong ER expression is associated with good response to hormonal treatment and strong PR expression favors survival, particularly in patients who are also ER positive (15,16). The Kaplan-Meier curves in the present study demonstrate that PR status is closely correlated with overall survival (Figs.…”

Section: Discussionsupporting

confidence: 61%

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

et al. 2017

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Abstract. In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1. 36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

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Section: Discussionsupporting

confidence: 61%

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

et al. 2017

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“…Paradoxically however, PR positive patients had better DFS. This result initially appears contradictory, but is in line with other published data [16,[21][22][23]. Low PR expression has been associated with low DFS in ER positive/Her2 negative patients [21], and poor outcome in the Luminal B subgroup [22].…”

Section: Discussionsupporting

confidence: 87%

“…Low PR expression has been associated with low DFS in ER positive/Her2 negative patients [21], and poor outcome in the Luminal B subgroup [22]. PR status may even be a powerful, independent prognostic variable in early breast cancer management [23].…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer – a Single Centre Study. (PPLB – 01)

Agrawal

Banswal

Saha

et al. 2016

Indian J Surg Oncol

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Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart from increasing breast conservation rates, also provides an opportunity to assess tumour response to chemotherapy, with Pathological Complete Response (pCR) described as an independent prognostic factor and a surrogate marker for better outcome and survival. Our primary aim was to identify clinical and pathological factors associated with pCR following NACT in patients with LABC treated at our institution. Our secondary aim was to analyze the impact of pCR and associated factors on disease free survival (DFS) and overall survival (OS). A retrospective analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013. Clinical and histological variables were analyzed for association with pCR (no invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier curves and Cox regression model was used for survival analysis. All values were twosided, and statistical significance was defined as p < 0.05. 240 patients were included. The median tumor size was 6 cm, with T4 disease in 49.8 %. 45 % of tumors were of low grade (G1 + G2) and 53.8 % of high grade (G3). Estrogen Receptor (ER) was positive in 70.8 %, progesterone receptor (PR) in 53.3 % and Her2 in 38.8 %. The preferred NACT regimen was sequential anthracycline and taxane and 88.8 % of patients received this regimen. Of 93 potential Her2 Positive patients, only 23 received trastuzumab. Overall 23.2 % patients had pCR. At median follow up of 21 months (range, 3-42), 16.3 % of patients had recurrent disease, and 6.7 % had died. High tumor grade (p = 0.04), PR negative status (p < 0.01) and trastuzumab treatment (p = 0.01) were significant predictors of pCR in univariate analysis. On multivariate analysis PR negativity (OR 3.2, 95 % CI = 1.6 to 6.04, p = 0.001) and Trastuzumab use (OR 0.24, 95 % CI = 0.1 to 0.6, p = 0.004) were significant. Patients with pCR had positive associations with survival (p < .02,OS& .02,DFS) and interestingly PR positivity had positive association with DFS (p = 0.02) in Kaplan-Meier curves. On Cox regression, PR positivity (HR = 0.3, p < 0.01) and pCR (HR = 0.2, p < 0.01) correlated with DFS, though not with early OS. for the PR positive patients were paradoxical. Though less likely to have pCR (15 %, vs 32 % if PR negative), they had better DFS (p = 0.02), and achieving pCR had no survival benefit in this group. In contrast, PR negative patients, irrespective of ER status, had a high pCR rate, and achieving pCR had survival advantage (p < 0.05,DFS& p < 0.02,OS). PR negative patients without pCR had the worst DFS (p < 0.01) among all. High grade and Trastuzumab treatment as predictors of pCR, and pCR as a surrogate marker for survival are well recognized, and are supported by our findings. In present cohort, PR negativity showed prognostic importance independent of ER status. However these results were derived from sub-group, posthoc analysis of data from a pre-existing cohort, without 'apriori' hypothesis for survival analy...

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“…104 PR expression correlated inversely with HER2 overexpression, suggesting the loss of PR in ER-positive tumors may be a marker for an activated EGFR/HER2 pathway. 6,105 Patients with ER þ /PR À/ HER2 þ tumors have a reduced breast cancer-specific survival compared with patients with ER þ /PR þ /HER2 þ . 83 A recent study showed that the survival of patients with ER þ /PR þ / HER2 þ tumors was superior to those with ER þ /PR À /HER2 þ tumors across all stages, confirming that loss of PR is an unfavorable event.…”

Section: Her2-positive Bcmentioning

confidence: 99%

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Tang¹,

Tse

2016

Archives of Pathology &Amp; Laboratory Medicine

122

103

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Context.-The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basallike subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.Objective.-To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.Data Sources.-Data were obtained from pertinent peer-reviewed English-language literature.Conclusions.-The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.

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Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study

Cited by 150 publications

References 42 publications

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer – a Single Centre Study. (PPLB – 01)

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

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