Discordance between Receptor Status in Primary and Metastatic Breast Cancer: an Exploratory Study of Bone and Bone Marrow Biopsies

Amir, Eitan; Ooi, Wei; Simmons, Christine; Kahn, Harriette J.; Christakis, Monique; Popovic, Snezana; Kalina, M.; Chesney, Alden; Singh, Gurmit; Clemons, Mark

doi:10.1016/j.clon.2008.08.005

Cited by 59 publications

(47 citation statements)

References 29 publications

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“…2 shows the discordance proportions reported for ER in each study included in the analysis. The heterogeneity between proportions ranged from 3% [37] to 62% [44] (I 2 = 91%, s 2 = 0.08, p < 0.0001). The metaanalytic pooled discordance proportion was 20% (95% CI: 16-35%).…”

Section: Resultsmentioning

confidence: 99%

A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

Aurilio

Disalvatore

Pruneri

et al. 2014

European Journal of Cancer

227

117

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Background: The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed. Methods: A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions. Results: We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I 2 = 91%, European Journal of Cancer (2014) 50, 277-289 A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m ScienceDirectj o u r n a l h o m e p a g e : w w w . e j c a n c e r . c o m p < 0.0001), PgR (I 2 = 79%, p < 0.0001) and HER2 (I 2 = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16-35%) for ER, 33% (95% CI: 29-38%) for PgR and 8% (95% CI: 6-10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004). Conclusion: Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.

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Section: Resultsmentioning

confidence: 99%

A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

Aurilio

Disalvatore

Pruneri

et al. 2014

European Journal of Cancer

227

117

View full text Add to dashboard Cite

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“…Although they are preliminary, these data are consistent with those reported in breast cancer for both ER and PR. In particular, several studies have shown that the receptor status of breast metastases may differ from that of the primary tumor, with the primary tumor being positive and metastases being negative in most cases (30,31). This finding may be explained by either the clonal selection of less-differentiated receptor negative cells during the metastatic process or the occurrence of a genetic drift during tumor progression (32).…”

Section: European Journal Of Endocrinologymentioning

confidence: 97%

Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

Vannucchi

Leo

Perrino

et al. 2015

European Journal of Endocrinology

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Background: Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. Methods: We studied the expression of estrogen receptor a (ERa or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. Results: ERa and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER-and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERa-positive primary tumors analyzed had ERa-negative metastatic lymph nodes. At the genetic analyses, BRAF V600E mutation was detected in 23.2% of the tumors

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“…Moreover, we report here for the first time a statistically significant correlation between previous systemic treatments and modifications in receptors' expression. Several studies have addressed the issue of concordance/ discordance in receptors expression between primary tumor and metastases [9,[12][13][14][15][16][17][18][19][20][21][22][23][24]. Published studies have found discordance rates for ER status ranging from 10.2% to 56%, PR status ranging from 24.8% to 48.6%, and HER2 status ranging from 2.9% to 16%.…”

Section: Discussionmentioning

confidence: 99%

Discordances in Estrogen Receptor Status, Progesterone Receptor Status, and HER2 Status Between Primary Breast Cancer and Metastasis

et al. 2013

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Background. The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. Methods. Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3ϩ in immunohistochemistry or if amplification ratio was Ͼ2 in fluorescent in situ hybridization. Results. From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p ϭ 4 ϫ 10), and HER2 in 4% of lesions (p ϭ .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed. Conclusions. This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting. TheOncologist2013;18: 667-674 Implications for Practice: Discordance in estrogen receptor and progesterone receptor expression between the primary breast tumor and the corresponding metastatic lesion was high (17% and 29%, respectively), whereas HER2 status remained stable (4% of discordance). Previous chemotherapy, and specifically anthracycline-based chemotherapy, was associated with a switch in estrogen receptor status. Further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting. In the era of a more personalized approach to medicine and of genomic investigations of tumors, reliable and recent evaluation of tumor prognostic and predictive factors remains a challenge. INTRODUCTIONThe treatment of metastatic breast cancer (mBC) is complex with few recognized therapeutic standards, particularly after the first line of treatment. Multiple fa...

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Discordance between Receptor Status in Primary and Metastatic Breast Cancer: an Exploratory Study of Bone and Bone Marrow Biopsies

Cited by 59 publications

References 29 publications

A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

Discordances in Estrogen Receptor Status, Progesterone Receptor Status, and HER2 Status Between Primary Breast Cancer and Metastasis

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