scholarly journals DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Philipp Jurmeister ◽  
Karsten Weber ◽  
Sonia Villegas ◽  
Thomas Karn ◽  
Michael Untch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Hormone Receptor ◽  
Receptor Expression ◽  
Proliferation Index ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Dna Methylation Profiling ◽  
Hormone Receptor Expression ◽  
Methylation Profiling

Abstract Background Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1–10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup. Results In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; “LowHR TNBC-like”). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; “LowHR HRpos-like”). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases. Conclusions We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.

scholarly journals Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Fabio Puglisi ◽  
Lorenzo Gerratana ◽  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Luca Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Effect ◽  
Hormone Receptor ◽  
Recurrence Risk ◽  
Receptor Expression ◽  
Phase Iii ◽  
Composite Measure ◽  
Node Positive ◽  
Hormone Receptor Positive ◽  
Dose Dense

AbstractThe GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

Predictive factors associated with a pathologic complete response in a Mexican HER2+ breast cancer population.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12630-e12630
Author(s):  
Raul Alejandro Andrade Moreno ◽  
José Fabián Martínez-Herrera ◽  
Geovani Amador ◽  
Raquel Gerson Cwilich ◽  
Juan Alberto Serrano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Factors ◽  
Hormone Receptor ◽  
Locally Advanced ◽  
Complete Response ◽  
Receptor Expression ◽  
Proliferation Index ◽  
Comprehensive Cancer Center ◽  
Lymph Node Status ◽  
Her2 Breast Cancer

e12630 Background: The current standard of treatment for locally advanced and early HER2+ breast cancer is the use of neoadjuvant chemotherapy (NAC) in combination with trastuzumab and pertuzumab. Mexican reports about its efficacy and predictive factors leading to pathological complete response (pCR) are scarce and few statistics are known. Methods: We performed a retrospective review of medical records of locally advanced and early HER2+ breast cancer patients who were treated with NAC in association with pertuzumab and trastuzumab. pCR was defined as the absence of residual invasive cancer cells in the breast and lymph nodes (ypT0/ypN0). Other histopathological features included Tumor type, estrogen, and progesterone receptor expression, HER2 status and Ki67. Clinical data included age, body mass index and number of metastatic nodes. Results: Thirty-five patients with early or locally advanced HER2+ breast cancer diagnosed and treated in a Comprehensive Cancer Center between January 2014 to June 2020 were included. The median age in the population was 47 years (range 28-79) with 20 patients under 50 years (57% of the total population). 40% of the patients were classified as overweight or obese at the time of diagnosis. The predominant histology was infiltrating ductal carcinoma (91%). The most frequent clinical stages were IIA, (34.2%) IIB (31.4%) and IIIA (22.8%). The population included patients with N0 (21.7%), N1 (56.5%), N2 (13%) and N3 (8.7%). Most tumors were larger than 2 centimeters at the time of diagnosis. T1 (17.4%), T2 (60.9%), T3 (17.4%) and T4 (4.3%). Most of the patients (77%) had a high proliferation index (Ki67 > 20). A total of 12 patients (34.3%) were hormone receptor (HR) negative and the rest (65.7%) were categorized as Triple Positive. The chemotherapy schemes used for NAC treatment were AC/THP (57.5%), THP (22.8%), TCHP (17.1%) and FEC/THP (2.7%) pCR was achieved in 60% of the patients. Patients with HR (-) achieved a pCR in 83% of the cases (10/12 patients) against 47.8% (11/23 patients) of the triple positive population. The Odds ratio (OR) for residual disease was 6.6 (95%CI 1.17-37.02) in the HR+ population. HR-/HER2+ tumors (p = 0.49) were independent predictors of pCR at multivariate logistic regression. No other variables including Ki67, BMI, age, tumor size, type of chemotherapy administered, and lymph node status were statistically significant. Conclusions: In this Mexican population there is a significant difference between the percentage of patients who achieve pCR in relation to the status of hormone receptors, favoring those patients with hormone receptor negative tumors. Nevertheless, most of the population achieves this benefit regardless of their hormone status, as HER2+ tumors showed sensitivity to chemotherapy and to the humanized anti-HER2 therapies. No other clinical or pathological variables were associated with pCR.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

scholarly journals Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elham Sajjadi ◽  
Konstantinos Venetis ◽  
Roberto Piciotti ◽  
Marco Invernizzi ◽  
Elena Guerini-Rocco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mismatch Repair ◽  
Hormone Receptor ◽  
Therapy Resistance ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Breast Cancers ◽  
Comprehensive Overview ◽  
Hormone Receptor Positive ◽  
Status Assessment

AbstractThe clinical outcome of patients with a diagnosis of hormone receptor (HR)+ breast cancer has improved remarkably since the arrival of endocrine therapy. Yet, resistance to standard treatments is a major clinical challenge for breast cancer specialists and a life-threatening condition for the patients. In breast cancer, mismatch repair (MMR) status assessment has been demonstrated to be clinically relevant not only in terms of screening for inherited conditions such as Lynch syndrome, but also for prognostication, selection for immunotherapy, and early identification of therapy resistance. Peculiar traits characterize the MMR biology in HR+ breast cancers compared to other cancer types. In these tumors, MMR genetic alterations are relatively rare, occurring in ~3 % of cases. On the other hand, modifications at the protein level can be observed also in the absence of gene alterations and vice versa. In HR+ breast cancers, the prognostic role of MMR deficiency has been confirmed by several studies, but its predictive value remains a matter of controversy. The characterization of MMR status in these patients is troubled by the lack of tumor-specific guidelines and/or companion diagnostic tests. For this reason, precise identification of MMR-deficient breast cancers can be problematic. A deeper understanding of the MMR biology and clinical actionability in HR+ breast cancer may light the path to effective tumor-specific diagnostic tools. For a precise MMR status profiling, the specific strengths and limitations of the available technologies should be taken into consideration. This article aims at providing a comprehensive overview of the current state of knowledge of MMR alterations in HR+ breast cancer. The available armamentarium for MMR testing in these tumors is also examined along with possible strategies for a tailored pathological characterization.

scholarly journals Endocrine Therapy in Premenopausal Hormone Receptor–Positive Breast Cancer

2016 ◽  
Vol 12 (11) ◽  
pp. 1148-1156 ◽  
Author(s):  
Amye J. Tevaarwerk ◽  
Kari B. Wisinski ◽  
Ruth M. O’Regan
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Systemic Therapy ◽  
Hormone Receptor ◽  
Randomized Trials ◽  
Early Stage ◽  
Premenopausal Women ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Systemic therapy for premenopausal women with hormone receptor–positive breast cancer has evolved in the last 5 years, but critical questions remain. Recent randomized trials have demonstrated a benefit for the addition of ovarian suppression to endocrine therapy in patients with breast cancers considered to be at high risk for recurrence, whereas those with lower-risk cancers seem to have a favorable outcome with tamoxifen alone. Two large randomized trials have demonstrated a benefit for extending adjuvant tamoxifen beyond 5 years. Currently the choice of systemic therapy is selected empirically but molecular profiling may, in the near future, provide a more conclusive means of selecting an endocrine therapeutic approach for premenopausal patients. Given that a significant subset of hormone receptor–positive cancers are intrinsically resistant to endocrine agents, as well as the finding that inhibiting cyclin-dependent kinases 4 and 6 and mammalian target of rapamycin appears to potentially reverse this resistance in patients with metastatic disease, evaluation of these agents in the early-stage setting is ongoing.

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