Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases

Aitken, Sarah J.; Thomas, Jeremy; Langdon, Simon P.; Harrison, David J.; Faratian, Dana

doi:10.1093/annonc/mdp427

Cited by 149 publications

(127 citation statements)

References 43 publications

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“…High expression of these receptors is associated with higher incidence of lymph node metastasis in breast cancer patients [116,117]. A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease indicating a organotropy [118]. This concept of organ site specificity corroborates the hypothesis, that lymph node metastases do not further spread or if they do only into lymph nodes down stream the metastatic one.…”

Section: Do Lymph Node Metastases Metastasize?supporting

confidence: 66%

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

Gerber

Heintze

Stubert

et al. 2011

Breast Cancer Res Treat

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Evaluation of axillary lymph node status by sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND) are an inherent part of breast cancer treatment. Increased understanding of tumor biology has changed the prognostic and therapeutic impact of lymph node status. Non-invasive imaging techniques like axillary ultrasound, FDG-PET or MRI revealed moderate sensitivity and high specificity in evaluation of lymph node status. Therefore, they are not sufficient for lymph node staging. Otherwise the impact of remaining micrometastases and even macrometastases for prognosis and treatment decisions is overestimated.Considering tumor biology, the distinction of axillary metastases in isolated tumor cells (ITC, pN0[i+]); micrometastases (pN1mi), and macrometastases (pN1a)

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Section: Do Lymph Node Metastases Metastasize?supporting

confidence: 66%

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

Gerber

Heintze

Stubert

et al. 2011

Breast Cancer Res Treat

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“…Various studies have reported that the receptor status of metastatic breast cancer may differ from that of the primary tumor (1-4). Aitken et al (14) reported that metastatic lymph node receptor status may be a more accurate parameter for guiding adjuvant therapy. Thus, it is necessary to understand the alterations in tumor phenotype for further therapeutic decision making.…”

Section: Discussionmentioning

confidence: 99%

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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“…Immunofluorescence for ERa was carried out using methods previously described (28). For slide staining, 3-mm TMA slides were deparaffinized and antigen retrieved by pressure cooking in antigen retrieval buffer (sodium citrate, pH 6.0).…”

Section: Immunofluorescencementioning

confidence: 99%

“…A detailed description of the AQUA HistoRx methodology is available elsewhere (28,29). Pan-cytokeratin antibody was used to identify infiltrating tumor cells, DAPI counterstain to identify nuclei, and Cy5-tyramide detection to target for compartmentalized (tissue and subcellular) analysis of tissue sections.…”

Section: Aqua Automated Image Analysismentioning

confidence: 99%

Trastuzumab and Pertuzumab Produce Changes in Morphology and Estrogen Receptor Signaling in Ovarian Cancer Xenografts Revealing New Treatment Strategies

Faratian

Zweemer

Nagumo

et al. 2011

Clinical Cancer Research

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Purpose: The aim of this study was to investigate the antitumor effects of HER2-directed combination therapy in ovarian cancer xenograft models to evaluate their potential. The combinations of trastuzumab and pertuzumab, and trastuzumab and aromatase inhibitor therapy were investigated.Experimental Design: The effects of trastuzumab, pertuzumab, and letrozole on growth response, apoptosis, morphology, and gene and protein expression were evaluated in the SKOV3 ovarian cancer cell line xenograft and a panel of five human ovarian xenografts derived directly from clinical specimens.Results: The combination of HER2-directed antibodies showed enhanced antitumor activity compared with single antibody therapy in the SKOV3 xenograft model. Apoptosis, morphology, and estrogenregulated gene expression were modulated by these antibodies in both spatial and temporal manners. A panel of ovarian cancer xenografts showed differential growth responses to the combination of trastuzumab and pertuzumab. High HER2 expression and increasing HER3 protein expression on treatment were associated with growth response. In trastuzumab-treated SKOV3 tumors, there was a change in tumor morphology, with a reduction in frequency of estrogen receptor alpha (ERa)-negative clear cell areas. Trastuzumab, but not pertuzumab, increased expression of ERa in SKOV3 xenografts when analyzed by quantitative immunofluorescence. ERa and downstream signaling targets were modulated by trastuzumab alone and in combination. Trastuzumab enhanced the responsiveness of SKOV3 xenografts to letrozole when given in combination.Conclusions: These data suggest that trastuzumab in combination with pertuzumab could be an effective approach in high HER2-expressing ovarian cancers and could also enhance sensitivity to endocrine therapy in ERa-positive ovarian cancer. Clin Cancer Res; 17(13); 4451-61. Ó2011 AACR.

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Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases

Abstract: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

Cited by 149 publications

References 43 publications

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?

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

Trastuzumab and Pertuzumab Produce Changes in Morphology and Estrogen Receptor Signaling in Ovarian Cancer Xenografts Revealing New Treatment Strategies

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