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

Mellouli, Manel; Graja, Soumaya; Kridis, Wala Ben; Ayed, H. Ben; Makni, Saadia; Triki, Mouna; Khanfir, Afef; Boudawara, T.; Kallel, Rim

doi:10.1016/j.anndiagpath.2022.152044

Cited by 6 publications

(3 citation statements)

References 44 publications

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“…Its loss seems to be associated with lower overall survival, due to a hypothetic protective role of this receptor against metastatic spread [21]. Additionally, ER loss in metastatic sites may be associated with a worse prognosis and reduced overall survival [19,22]. Acquisition of HER2 expression in metastatic tissue is a known mechanism of endocrine resistance and leads to an increase in disease aggressiveness, yet it does not affect survival given the effective therapies available [19].…”

Section: Discussionmentioning

confidence: 99%

More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

Martorana,

Di Grazia,

Rosano

et al. 2023

Medicina

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Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously defined with different molecular profiles: (i) luminal androgen receptor (LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA). Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undefined prognosis and clinical behavior. Here, we report a case of a woman affected by recurring LAR TNBC, which underwent phenotypic changes throughout its natural history. After the initial diagnosis of LAR breast cancer, the patient experienced local recurrence with strong expression of the estrogen receptor. Due to this finding, she started treatment with a CDK4/6-inhibitor and an aromatase inhibitor, followed by oral vinorelbine, both with dismal outcomes. Then, she received everolimus and exemestane, which determined temporary disease stabilization. An extensive NGS analysis of tumor tissue showed PIK3CA and HER2 mutations. Our case is consistent with previous reports of LAR breast cancer and underlines the potential utility of re-biopsy and molecular testing in breast cancer (BC), especially in rare subtypes.

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Section: Discussionmentioning

confidence: 99%

More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

Martorana,

Di Grazia,

Rosano

et al. 2023

Medicina

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“…Oncologists now classify invasive breast cancer based on immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation factor Ki67, which not only provides prognostic information but it is also crucial for predicting treatment sensitivity. However, previous studies have reported changes in immunohistochemical expression of these four biomarkers between primary and metastatic tumors, and there may be even a significant prognostic impact of phenotype conversion (Lindstrom et al 2012 ; Mellouli et al 2022 ). Discordance in these tumor biomarkers has been reported due to analytical error, intratumoral heterogeneity, selective pressure of therapy and cellular clonal evolution (Shiino et al 2022 ).…”

Section: Introductionmentioning

confidence: 98%

Biomarker conversion from primary breast cancer to synchronous axillary lymph node metastasis and neoadjuvant therapy response: a single-center analysis

Ding,

Li,

Liu

et al. 2024

J Cancer Res Clin Oncol

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Purpose The biomarker characteristics of breast cancer plays an important role in predicting treatment sensitivity. The aim of the present study was to compare immunohistochemical profiles (ER, PR, HER2, and Ki67) between the primary tumor and synchronous axillary lymph node metastasis and investigate the subsequent effects on neoadjuvant therapy response. Methods A total of 358 patients with pathologically confirmed synchronous axillary lymph node metastasis at first diagnosis and treated by neoadjuvant therapy at Peking University First Hospital from January 1, 2013 to December 31, 2022 were included in this retrospective study. Clinicopathologic data, especially receptor status in primary and metastatic foci, was collected for each case. Results Change of ER, PR, HER2, and Ki67 expression was observed in 5.9%, 8.7%, 12.6%, and 17.3% of patients, respectively. HR discordance was observed more frequently when the ER status (p = 0.023) or PR status (p = 0.010) of primary tumor was negative, while HER2 discordance seemed to be more frequent when the HER2 status of primary tumor was HER2-0 or HER2-low (p < 0.001). Patients with loss of HR-positivity (positive to negative) responded to neoadjuvant chemotherapy better compared to those with stable positive HR expression (50% vs. 11.1%, p = 0.0017). A significantly decrease in pCR rate was observed in patients with unstable HER2 status, but not in the HER2-0/HER2-low subgroup. Conclusion Receptor discordance between primary tumor and synchronous axillary LNM appears to already exist before any anti-tumor therapy. This instability has limited clinical impact on the choice of neoadjuvant therapy at current stage, but further investigation is warranted with the incremental application of endocrine drugs and ADCs in neoadjuvant therapy.

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“…Heterogeneity has been demonstrated in hormone and HER2 receptor expression [25,26]. Also, metastatic breast cancer histological subtype differs from the original tumor classification in approximately 17% of recurrent MBC patients when they switch from lobular to ductal and vice versa [27].…”

Section: Introductionmentioning

confidence: 99%

Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives

Ndlovu,

Lawal,

Mokoala

et al. 2024

IJMS

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Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decision-making, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standard-of-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches’ relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation.

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

Cited by 6 publications

References 44 publications

More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

Biomarker conversion from primary breast cancer to synchronous axillary lymph node metastasis and neoadjuvant therapy response: a single-center analysis

Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives

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