Discordance In Receptor Status Research Articles

Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis

BackgroundThe tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival. Materials and methodsIt was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis. ResultsOur study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors. ConclusionThis study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.

Discordance of Diagnostic Core Biopsy and Final Histopathology Performed after Surgical Resection of Breast Cancer

Objective: To determine the frequency of discordance of receptor status in our breast cancer patients, find out its causes, and suggest remedial measures.&#x0D; Study Design: Retrospective longitudinal study.&#x0D; Place and Duration of Study: Breast clinic and Radiation Oncology Department of Combined Military Hospital Rawalpindi Pakistan from Jan 2018 to Nov 2021.&#x0D; Methodology: Estrogen Receptor, Progesterone Receptor and Her2 Neu status differences between diagnostic tru-cut biopsy and surgical specimen were compared.&#x0D; Results: Receptor status between initial core biopsy and final histopathology of 63 patients were compared. Discordance rates of 05 (7.90%), 13 (20.60%) and 12 (19%) were noted for Estrogen receptor, progesterone receptor and Her2, respectively. The highest discordance noted was for the progesterone receptor, followed by the HER2 receptor and the Estrogen receptor.&#x0D; Conclusion: The highest discordance noted was for the progesterone receptor, followed by the HER2 receptor and the Estrogen receptor. Further studies are required to know more about the causes of receptor status discordance, its impact on treatment decisions and its impact on disease progression and survival.

Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics

Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. We developed a precision oncology platform that combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, and molecular tumor boards, with the goal of improving cancer management through enhanced understanding of the entire cancer ecosystem within each patient. We describe this integrative approach using comprehensive analytics generated from serial-biopsied lesions in a metastatic breast cancer patient. The serial biopsies identified remarkable heterogeneity among metastatic lesions that presented clinically as discordance in receptor status and genomic alterations with mixed treatment response. Based on our study, we highlight clinical scenarios, such as rapid progression or mixed response, that indicate consideration for repeat biopsies to evaluate intermetastatic heterogeneity (IMH), with the objective of refining targeted therapy. We present a framework for understanding the clinical significance of heterogeneity in breast cancer between metastatic lesions utilizing multi-omic analyses of serial biopsies and its implication for effective personalized treatment.

Discordance in Biomarker Expression in Breast Cancer After Metastasis: Single Center Experience in India.

PURPOSEBiomarker—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) —discordance plays an essential role in the management and prognosis of patients with metastatic breast cancer. Rates of discordance have been previously reported around 12% to 35%, 30% to 50%, and 5% to 15%, respectively, in Western literature. Data are sparse regarding the same from developing countries, such as India.METHODSWe performed an ambispective review of paired biomarker status in patients with breast cancer—stage I, II, and III as per American Joint Committee on Cancer, 7th edition—who developed metastasis at recurrence (N = 103 patients). Biomarker status and clinical and radiologic parameters were documented at baseline and subsequent follow-up.RESULTSDiscordance was present in 21.3% for ER, 29.1% for PR, and 15.5% for HER2/neu receptor. In our cohort, 7.8% had positive to negative ER and 13.6% negative to positive. Whereas 21.4% had positive to negative PR, 7.8% had negative to positive PR. Approximately 6.8% had positive to negative HER2/neu receptor and 8.7% negative to positive. In our cohort, 41 patients (40%) had single-site metastasis—bone, 15.5%; lung, 11.7%; nonregional lymph node, 7.8%; liver, 3.9%; and brain, 0.97%. More than one site of metastasis was present in 62 patients (60%). The most common sites of metastasis were visceral—lung and liver—followed by bone, nonregional lymph node, skin, and brain.CONCLUSIONThe current study demonstrated that metastatic disease evolution in breast cancer is characterized by change in the tumor biology, which leads to discordance in receptor status. Repeat biomarker studies at metastatic recurrence is warranted, especially if treatment plans include hormone and targeted therapy.

Influences of adjuvant treatments in hormone receptor positive breast cancer on receptor conversion in recurrent breast cancer.

To examine influences on the receptor status of a local cohort of patients with recurrent breast cancer after primary diagnosis of hormone receptor positive breast cancer. We retrospectively analyzed 2078 female patients with primary hormone receptor positive breast cancer treated at the university hospital of Wuerzburg between 2000 and 2013. Main focus was on discordance in receptor status in recurrent disease. 196 patients with the primary diagnosis of hormone receptor positive breast cancer developed recurrent disease. 29.1% of patients revealed discordance in estrogen receptor (ER), progesterone receptor (PgR) or HER2 receptor (ER+ to -: 33.3%; PgR+ to -: 59.6%; HER2+ to -: 8.8%; HER2- to +: 17.5%). Aggressive tumor biology such as low grading or involvement of axillary lymph nodes showed increased risk of receptor conversion in relapse. Premenopausal patients with adjuvant application of tamoxifen and the application of chemotherapy had a significantly lower risk for the development of ER negative recurrent disease. Receptor changes to ER and PgR negativity in recurrent disease showed a trend to worse overall survival (OS). Histological analysis of recurrent disease is indispensable, since one-third of patients with hormone receptor positive breast cancer develop change in the receptor status.

Profile and Outcome of Supraclavicular Metastases in Patients with Metastatic Breast Cancer: Discordance of Receptor Status Between Primary and Metastatic Site.

Breast cancer is a heterogenous and complex disease. A rare site of metastatic breast cancer disease is the neck. Data about supraclavicular metastases in patients with metastatic breast cancer are still lacking. Hence, our study aimed to analyze histological subtypes of supraclavicular metastases compared to the primary site. This was a retrospective hospital-based cohort study of patients with breast cancer who developed supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed by biopsy or diagnostic lymph node extirpation. Histological subtypes were analyzed and Kaplan-Meier estimates were calculated for overall survival. A total of 20 patients were included in the analysis. The majority of the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20 patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20 patients and basal-like in 4/20 patients. Total discordance rates for estrogen receptor, progesterone receptor and HER2 between primary and metastatic tumors were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%, whereas the 5-year survival after the onset of neck metastasis was 45%. As a rare site of metastatic breast cancer, supraclavicular metastases are associated with a worse median overall survival from their onset. The high rate of discordance of histological subtype stresses the necessity for biopsies in patients with supraclavicular metastasis.

Role of biological heterogeneity in recurrent and metastatic breast cancer

Breast cancer (BC) is a heterogeneous tumor, the biological characteristics of which vary with its growth and progression. Information on key tumor receptors (ER, PR, HER2, and Ki-67) is the basis for individualizing the diagnostic and treatment algorithm at all BC stages; however, the feasibility of biopsy of distant metastases and the re-testing of the biological subtype of BC in its suspected progression are being actively discussed in clinical practice. This review presents an update on the features of metastasis in different biological BC subtypes and assesses the clinical and prognostic role of biopsy of distant metastases in the lung, bones, liver, and brain. It shows the frequency of discordance in receptor status between primary and recurrent tumors at different sites of metastases, as well as the impact of changes in receptor status on survival rates in different biological BC subtypes. The relevance of performing biopsies in BC progression is shown to be beyond question, because it makes it possible to confirm the fact that the disease progresses, to re-test the biological subtype of recurrent BC, and to find new targets that allow the most effective drug treatment regimens to be used.

Patients with Concordant Triple-Negative Phenotype between Primary Breast Cancers and Corresponding Metastases Have Poor Prognosis

PurposeWe investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases.MethodsA total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triple-negative phenotype (TNP) or non-TNP. Concordance and discordance was determined by whether there was a change in receptor status or phenotype between primary and metastatic lesions.ResultsThe rates of discordance between primary breast cancer and metastatic lesions were 18.1%, 25.0%, and 10.3% for ER, PR, and HER2, respectively. The rates of concordant non-TNP, concordant TNP and discordant TNP were 65.9%, 20.9%, and 13.2%, respectively. Patients with concordant ER/PR-negative status had worse postrecurrence survival (PRS) than patients with concordant ER/PR-positive and discordant ER/PR status (p=0.001 and p=0.021, respectively). Patients who converted from HER2-positive to negative after distant metastasis had worst PRS (p=0.040). Multivariate analysis showed that concordant TNP was statistically significant factor for worse PRS (p<0.001).ConclusionDiscordance in receptor status and tumor phenotype between primary breast cancer and corresponding metastatic lesions was observed. Patients with concordant TNP had worse long-term outcomes than patients with concordant non-TNP and discordant TNP between primary and metastatic breast cancer. Identifying the receptor status of metastatic lesions may lead to improvements in patient management and survival.

Discordance of receptor status in breast cancer throughout tumor progression and the associated prognostic implications: A case report and review of the literature

The receptor status of a breast cancer, including estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor 2 (HER2), play a critical role in the development of a treatment plan. Typically, the primary receptor status has been used to make treatment decisions at the time of relapse, which occurs in approximately 20% of early-stage breast cancers [1]. However, multiple studies, including both prospective and retrospective, have shown that receptor status is dynamic and is unstable throughout tumor progression and during advanced stage disease [1,2,7]. National Comprehensive Cancer Network (NCCN) guidelines recommend that breast cancer patients with relapsed disease be re-biopsied secondary to the possibility of change in receptor status. Change in receptor status not only has clinical relevance when deciding on a treatment plan, it also has an impact on survival [1,2,4,7]. Of the 20% of patients that will relapse, up to one-third will have discordance between their original ER/PR receptor status and relapsed status, and up to 15% have discordance with regard to HER2 status [1]. Loss of receptor status is associated with a decrease in overall survival [1,2]. We present a case in which receptor status changed 3 times

Prognostic implications of receptor discordance between primary and recurrent breast cancer.

Discordance rates of hormone receptor (HR) and human epidermal growth factor-2 (HER2) status between primary and recurrent breast cancer were reported to be in the wide range of 10-40 %, although its prognostic relevance remains to be elucidated. Fifty-five breast cancer patients had biopsies or resections of recurrent lesions. Pathological assessments of the HR and HER2 status of primary and recurrent lesions were performed in a single laboratory at Keio University Hospital. Tumors were classified as luminal (HR+ and HER2-), luminal/HER2 (HR+ and HER2+), HER2 (HR- and HER2+), or triple negative (HR- and HER2-). Discordance rates in estrogen receptor (ER), progesterone receptor (PgR) and HER2 status between primary tumors and recurrent lesions were 16.4, 30.9 and 10.2 %, respectively. Overall, 14 patients (25.5 %) changed subtypes at recurrent lesions. Patients with a gain in ER and PgR status had a significantly longer disease-free interval compared with the corresponding concordant-negative patients (ER: 99.0 vs. 18.5 months, p = 0.037, PgR: 141.0 vs. 24.4 months, p = 0.011). Patients with a loss of HER2 status experienced a trend toward shorter time to progression, compared with patients who maintained HER2 positivity (4.0 vs. 18.4 months, p = 0.051). Discordance in receptor status between primary and recurrent breast cancers were seen in 10-30 %. A gain in HR status was significantly associated with better prognosis.

Breast cancer during follow-up and progression – A population based cohort on new cancers and changed biology

BackgroundEmerging data indicate an important role for biopsies of clinically/radiologically defined breast cancer ‘recurrences’. The present study investigates tumour related events (relapses, other malignancies, benign conditions) after a primary breast cancer diagnosis. Patients and methodsThe cohort includes 2102 women, representing all patients, with primary invasive breast cancer during 2000–2011 in the county of Värmland, Sweden. A comparative analysis of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation (Ki67) between the primary tumour and the relapse was performed and related to outcome. ResultsWith a mean follow-up time of 4.8years, 1060 out of 2102 patients have had a biopsy taken after the initial breast cancer diagnosis demonstrating 177 recurrences, 93 other malignancies (colorectal, lung, skin), 40 cancer in situ (skin, breast) and 857 benign lesions. Approximately 70% (177 out of 245) of all cases of relapsed breast cancer underwent a biopsy during this time period. For patients with recurrences, ER (n=127), PR (n=101), HER2 (n=73) and Ki67 (n=55) status in both primary tumour and the corresponding relapse were determined. The discordance of receptor status was 14.2%, 39.6%, 9.6% and 36.3%, respectively. Loss of ER or PR in the relapse resulted in a significant increased risk of death (hazard ratio (HR) 3.62; 95% confidence interval (CI), 1.65–7.94) and (HR 2.34; 95% CI, 1.01–5.47) compared with patients with stable ER or PR positive tumours. The proportion of patients losing ER was bigger in the group treated with endocrine therapy alone or in combination with chemotherapy, 16.7% and 13.3%, respectively, compared with the group treated with chemotherapy alone or that which received no treatment 4.3% and 7.7%, respectively. ConclusionDiscordance of biomarkers between the primary tumour and the corresponding relapse was seen in 10–40% of the patients, adjuvant therapies seem to drive clonal selections. Patients with tumours losing ER or PR during progression have worse survival compared with patients with retained receptor expression.

Maintenance treatment of trastuzumab for patients with advanced breast cancer to achieve long term survival: two case reports and literature review.

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. The epidermal growth factor receptor (HER2) overexpressing breast cancers are designated as HER2-postive (HER2+) breast cancer and carry a particularly unfavorable prognosis. We present two cases of HER2-postive metastatic breast cancer (MBC) who are found to be a challenge to treat, especially due to the occurrence of brain metastasis. Trastuzumab-based therapy improves clinical outcomes, even if the patient has undergone multi-line treatment. These case reports also emphasize the importance of retesting HER2 status because it can be discordance in receptor status between primary and recurrent breast cancer.

Biopsy confirmation of metastatic sites in breast cancer patients: clinical impact and future perspectives.

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome, and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations, the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future, advances in targeted therapy will depend on the availability of metastatic tissue.

Re-biopsy in breast cancer recurrence: Is there really a clinical impact?

e11549 Background: Several retrospective studies and 3 prospective studies have shown discordance in receptor status between primary tumor and metastasis leading to a treatment modification in about one out of 7 patients. However, some clinicians report unpublished data suggesting that these findings are not observed in all centers. We did prospectively a biopsy at suspicion of first relapse in our center and evaluated the impact of this biopsy on the management of our patients. Methods: Thirty four patients underwent a biopsy between October 2011 and January 2013. Hormonal receptor status was determined by the same IHC methodology for primary and metastatic tissue. Primary tumors were reanalyzed if necessary with our current IHC technique. A change in ER or PgR status was considered clinically significant if quantitative staining changed from &lt;5 % to at least 10% of tumor cells expressing the hormonal receptor or if the opposite is observed. We tested HER2 status by IHC and/or FISH: HER2 3+ or 2+ and FISH positive cases were considered as HER2 positive. Results: Three of 34 patients were considered as screening failure. 1/31 (3.2 %) biopsies showed a benign disease, 2/31 (6.4 %) were non contributive and 5/31 (16 %) showed a metastasis of a second primary tumor. Two of these findings were totally unexpected according to clinical data. Changes in hormone receptor status were observed in 25 % but no change in HER2 status was observed. Time to recurrence was not significantly different between groups with or without modified hormonal status. No clinically significant complication was observed following the biopsies. Only patients presenting a second primary tumor had their management changed based on the new biopsy. Conclusions: We found discordance in hormone receptor status (25 %) but it did not change the treatment. Our study confirms the importance of re-biopsy in order to exclude benign disease or to find metastasis from an unknown and sometimes unexpected second primary tumor. Although our study does neither confirm changes in hormonal receptors resulting in the modification of the treatment strategy nor a change in HER2 status, our data suggest that a new biopsy at first relapse should be performed because unexpected second primaries can be discovered.

Discordant ER, PR, and HER2 status between primary and metastatic breast cancer as prognostic factor.

1039 Background: The receptor status including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) of metastases may be different from that of the primary breast cancer. This discordance of receptor status may influence patient prognosis. We investigated discordance of receptor status between primary breast cancer and distant metastases in the same patients and its effect on prognosis. Methods: ER, PR, and HER2 status in metastases were available in 173 patients. The receptor status was compared between primary tumors and metastases. Tumors were classified as triple-negative breast cancer (TNBC) or non-triple-negative breast cancer (non-TNBC) according to receptor status and as concordant and discordant depending on the difference of receptor status between primary and metastatic breast cancer. Survival analysis was performed depending on concordant or discordant receptor status. Results: Discordance for ER, PR, and HER2 was 18.5%, 23.7%, and 10.4%, respectively. Concordant non-TNBC and TNBC between primary tumors and metastases was 69.9% and 17.9%, respectively. Discordant TNBC was 12.1%. On multivariate analysis, patients with discordant TNBC had unfavorable survival compared with patients with concordant non-TNBC (relative risk 2.544, 95% confidence interval, 1.220-5.303, p = 0.013). The median survival after recurrence was 41.8 months for patients with concordant non-TNBC, 20.7 months for patients with concordant TNBC, and 19.9 months for patients with discordant TNBC (p &lt; 0.0001). Conclusions: The change of ER, PR, and HER2 status between primary and metastatic tumors occur and discordant TNBC is associated with poor survival.

Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-Institution analysis

Tumor phenotype may change during breast cancer progression. This study evaluates the prognostic impact of receptor discordance between paired primaries and recurrences. One hundred and thirty-nine patients underwent histological sampling of suspected breast cancer recurrence. All the pathology assessments [ER, PgR and human epidermal growth factor receptor 2 (HER2)] on both primaries and confirmed recurrences were performed at the same laboratory. A breast cancer recurrence was confirmed in 119 cases. Rates of discordance were 13.4%, 39% and 11.8% for ER, PgR and HER2, respectively. Ninety-two patients maintained the same tumor phenotype [i.e. the same hormone receptors (HR) and HER2 status], whereas 27 (22.7%) changed during progression. The loss of HR positivity and the loss of HER2 positivity resulted in a worse post-recurrence survival (P=0.01 and P=0.008, respectively) and overall survival (OS; P=0.06 and P=0.0002, respectively), compared with the corresponding concordant-positive cases. Tumor phenotype discordance was associated with worse post-recurrence and OS (P=0.006 and P=0.002, respectively); those cases who turned into triple-negative experienced the poorest outcome, respect to the concordant group (P=0.001, OS). We demonstrated for the first time an impact on OS of phenotype discordance between primary breast cancer and relapse. Among discordant cases, receptor loss resulted in the main determinant of poorer outcome.

Abstract P1-02-02: Receptor discordance in breast cancer recurrence: Is re-biopsy a necessity?

Abstract Background: Decision making on systematic treatment of patients with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. Recent prospective studies have investigated discordance in receptor status between the primary and metastatic tumor. We evaluated the discordance of receptor status between the primary and metastatic tumor and assessed the impact of re-biopsy on patient management. Methods: In breast cancer patients who underwent surgical resection of primary tumor and re-biopsy of metastatic tumor at Aichi Cancer Center hospital, we examined the discordance of ER status, PgR status, and HER2 status between the primary and metastatic tumor. For sampling of metastases, core needle biopsy (CNB), trans-bronchial lung biopsy (TBLB), or surgical resection was performed. And fine-needle aspiration biopsy was not used. The ER and PgR status were assessed using Allreds scoring system by IHC. These statuses were categorized as positive when the total score was more than two. HER2 expression status was tested by IHC and FISH. HER2 3+ by IHC, or 2+ and FISH positive were judged as HER2 positive. Results: 48 patients underwent re-biopsy from 2003 to 2012. Twenty-eight were loco-regional (local: 25, Supraclavicular: 2, Axilla: 1) and 21 were distant (Lung: 14, Liver: 6, Bone: 1). Discordance in ER, PgR, or HER2 between the primary and metastatic tumor were 6.2% (3/48), 16.7% (8/48), and 4.2% (2/48), respectively. One patient had discordance on re-biopsy with initial triple negative primary tumor (1/5, 20%). 11/48 patients (22.9%) changed the molecular subtype (Group A), and 37/48 patients (77.1%) did not change (Group B). Time to recurrence (TTR) was significantly longer in Group A than Group B (82.3 months vs 51.2 months, p = 0.04). No significant difference in re-biopsy techniques (CNB and TBLB vs surgical resection), metastatic lesions (loco-regional vs distant), and adjuvant therapy were observed between Group A and Group B. Conclusions: Our results show the low level of discordance for ER and HER2 between the primary and metastatic tumor. But re-biopsy should be considered in the patients with long TTR, since it is likely to impact treatment choice. Further study is needed to determine the value of re-biopsy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-02-02.

Abstract P2-05-07: Comparison of hormone receptor and HER-2 expression in primary breast cancers and sentinel lymph node metastases

Abstract Background: Recently, it is a hot topic that the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) may differ between the primary tumors and the paired recurrent metastatic tumors. On the other hand, the concordance of the ER, PR, and HER2 status between the primary tumor and ipsilateral axillary lymph node metastases is reported to be high in previous study. However, in these reports, the majority of lymph nodes metastases examined are macrometastases obtained from axillary lymph node dissection. The aim of the present study is to compare the ER, PR, and HER2 status of the primary breast tumors with that of sentinel lymph node micrometastases and macrometastases. Methods: A total of 770 breast cancer patients underwent sentinel lymph node biopsy between 2006 and 2010 at our hospital. Among them, 87 patients who had only one node positive were eligible for our study. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Result: We analyzed 76 patients with 50(66%) patients with macrometastasesn and 26 (34%) micrometastases, except 11 cases those were indeterminate for IHC. ER status of primary tumor and the paired metastatic lymph node were almost full concordance except one case, in which ER was negative in primary tumor but ER was positive in lymph node. Discordance for PR was 15.8% (n = 12). Among these, six patients had PR-positive on primary and PR-negative in lymph node while six patients had PR-negative in primary and PR-positive in lymph node. Discordance for HER2 between primary tumor and metastatic lymph node was 5.3% (n = 4). Among these, three had negative in primaries and positive in lymph nodes while one had positive in primary and negative in lymph node. A discordance between primary and lymph node in HER2, ER, or PR status was observed in 14 of 67 (18.4%) cases. Conclusions: The concordance in HER2, ER, and PR was high between the primary tumor and sentinel lymph nodes. However some cases had discordance of receptor status and these result may cause of discordance for distant metastases or poor prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-07.

Abstract P6-05-05: Triple receptor comparison between primary breast cancer and metachronous or synchronous liver metastasis

Abstract Background: Decisions about systemic treatment in women with metastatic breast cancer are currently based on the presence of estrogen receptors (ER), progesterone receptors (PR) or Human Epidermal growth factor Receptor 2 (HER2 receptors) in the primary tumor. Recently, several studies have reported significant discordances in ER, PR and HER2 status between the primary tumor and metastatic lesions and this may vary by metastatic site. Prognostic implications remain unclear although alterations in ER, PR and/or HER2 can influence metastatic management. This study represents one of the largest studies evaluating how frequent receptor discordances occur in liver metastasis, whether this alters therapeutic options and impacts prognosis. Patients and methods: 246 breast cancer patients with histological confirmed liver metastasis were analyzed in this retrospective study. Immunohistochemistry (IHC) and/or FISH were used to determine ER, PR and HER2 receptor status. We excluded patients when comparison between receptors of primary tumor and metastasis was impossible due to missing data (n = 85), when liver metastasis did not originate from breast cancer (n = 36) and when pathology was obtained from autopsy specimens (n = 38). Results: 87 patients had matched tissue samples of primary tumor and liver metastasis with possible comparison of at least one of the receptors. Table 1 summarizes changes in ER, PR, HER2 between primary and metastatic lesion. Discordance in receptor status was associated with shorter time to death (63.3 months) compared to the concordant group (75.5 months). Conclusions: A significant proportion of ER and PR show discordance between primary tumor and liver metastasis. However we could not establish the same level of discordance for the HER2 receptors as in other studies. In general, only about 1 in 5 patients gained new (endocrine or targeted) therapeutic options. Tissue confirmation remains important to evaluate whether metastatic disease has become endocrine insensitive (in approximately 1 in 5 patients), avoiding unnecessary delay in chemotherapy. Discordance in receptors may be associated with inferior prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-05.

To Biopsy or Not to Biopsy: Is That the Only Question?

The clinical effects of discordance in receptor status between primary and metastatic breast cancer lesions are discussed in relation to the study of Macfarlane et al. published in this issue of The Oncologist.