Histologic subtypes of ductal intraepithelial neoplasia (DIN) of the breast: Characteristic associations and biology

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 633-633
Author(s):  
J. D. Schwartz ◽  
C. Christy ◽  
B. Grube ◽  
M. Rishi ◽  
F. Tavassoli ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Intraepithelial Neoplasia ◽  
Invasive Cancer ◽  
Biological Behavior ◽  
Low Grade ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Histologic Subtype ◽  
Hormone Receptor Positive ◽  
Histologic Subtypes

633 Background: Most invasive breast cancers are associated with more than one histologic subtype of DIN. The clinical and biologic significance of these DIN subtypes is under-appreciated. Methods: We reviewed 853 cases of DIN diagnosed at our University based Breast Center between 2003 and 2008, 568 (67%) of which were associated with an invasive cancer. Cases of pure invasive cancer without DIN were excluded. Results: A single histologic subtype was present in 41% of the cases, two subtypes in 43%, and three in 16%. The most common DIN subtypes present were solid (52%) and cribriform (50%), while the comedo (18%), micropapillary (11%), papillary (9%) and flat (6%) subtypes were less common. Comedo and solid DIN were frequently found together (Odds ratio [OR]) for coexpression 1.94, p< .001) as were micropapillary and papillary subtypes (OR 2.58, p< .005). Comedo DIN was much less likely to be found with papillary (OR .24, p< .005), flat (OR .34, p< .05), cribriform (OR .42, p< .001) or micropapillary (OR .48, p< .05) subtypes. We also examined multiple biological parameters and their association with the different DIN subtypes as shown in the table below. Solid and comedo subtypes tend to be hormone receptor negative, Her2 positive and high grade while the cribriform subtype tends to be hormone receptor positive, Her2 negative and low grade. Papillary and comedo DIN are most likely to be larger lesions. Papillary DIN is least likely to be associated with an invasive cancer. Conclusions: The histologic architecture provides clues to the underlying molecular changes and biological behavior of DIN. This study will begin to help us understand the molecular basis for the different histologic subtypes of DIN, their different clinical behaviors and tendencies to progress to invasive cancer. [Table: see text] No significant financial relationships to disclose.

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 Low Prevalence of HER2-Positive Breast Carcinomas among Screening Detected Breast Cancers

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1578
Author(s):  
M. Ángeles López-García ◽  
Irene Carretero-Barrio ◽  
Belén Pérez-Míes ◽  
Miguel Chiva ◽  
Carolina Castilla ◽  
...  
Keyword(s):  
Racial Differences ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Lower Prevalence ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Her2 Positive ◽  
Screening Programs ◽  
Hormone Receptor Positive

Conflicting results have been reported regarding the prevalence of screen-detected human epidermal growth factor receptor 2 (HER2)-positive breast carcinomas and non-screen detected HER2-positive breast carcinomas. To address this issue, we evaluated the prevalence of HER2-positive breast carcinomas in two independent regional screening programs in Spain. The clinicopathologic and immunohistochemical characteristics of 479 (306 and 173) screen-detected breast carcinomas and 819 (479 and 340) non-screen-detected breast carcinomas diagnosed in women between 50 and 69-year-olds were compared. The prevalence of HER2-positive breast carcinomas was 8.8% and 6.4% in the two series of screen-detected tumors, compared with 16.4% and 13% in non-screen-detected carcinomas. These differences were statistically significant. This lower prevalence of HER2-positive in-screen-detected breast carcinomas was observed in both hormone receptor positive (luminal HER2) and hormone-receptor-negative (HER2 enriched) tumors. In addition, a lower prevalence of triple-negative and a higher prevalence of luminal-A breast carcinomas was observed in screen-detected tumors. Moreover, a literature review pointed out important differences in subrogate molecular types in screen-detected breast carcinomas among reported series, mainly due to study design, technical issues and racial differences.

Oncotype DX score in hormone receptor-positive/HER2-positive breast cancer: A SEER analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12044-e12044
Author(s):  
Ayman Qasrawi ◽  
Zin Myint ◽  
Yanal Mufeed Alnimer ◽  
Edward H. Romond
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Early Stage ◽  
Nodal Status ◽  
Oncotype Dx ◽  
National Database ◽  
Histologic Subtype ◽  
Hormone Receptor Positive ◽  
Histologic Subtypes

e12044 Background: The recurrence score Oncotype DX (RS) predicts the need for adjuvant chemotherapy in hormone receptor positive (HR+) early stage breast cancer (BC). However, it has not been validated for HR+/HER2+ BC cases. We aim to evaluate the results of RS in HR+/HER2+ BC by using the Surveillance, Epidemiology, and End Results Program (SEER) national database. Methods: We identified patients with non-metastatic HR+/HER2+ BC with reported RS scores from the national SEER database between 2010 and 2015. Data obtained included demographics, histologic subtypes, grading, tumor size, nodal status, HR status and overall survival (OS) outcomes. RS scores were divided into low/intermediate (≤30) and high ( > 30). Histologic subtypes were further categorized into favorable (lobular, tubular, mucinous, and cribriform) and unfavorable (infiltrating ductal, mixed ductal, and micropapillary). We used Kaplan-Meier & Cox regression to analyze the survival outcomes. Logistic regression analysis was used to analyze the correlation between variables and different RS scores. Results: A total of 1537 patients were included. Median age was 61 (25-90). Majority of the patients presented with node negative disease (85%), low/intermediate grade (71%), tumor size < 20 mm (73%), unfavorable histology (89%), and only 15% had negative progesterone receptor (PR –). High RS score ( > 30) was seen in 24% of cases. After a median follow-up of 38 m (1-72), the five-year OS was 94.5%. Chemotherapy was given to 71% and 35% of those with RS > 30 and ≤30, respectively. There was a strong correlation between age > 60 ([hazard ratio, HR] = 4.9, p < 0.0001) and RS > 30 (HR = 2.4, p = 0.004) with worse outcomes on multivariate analysis. However, there were no associations between histologic subtype, tumor size, grade, nodal status and chemotherapy with survival. Tumor size > 20 mm (OR = 1.5), unfavorable histology ([odds ratio, OR] = 3.5), PR – (OR = 4.3) and high grade tumors (OR = 4.5) were independent predictors of RS > 30 (p < 0.0001). Conclusions: Our study shows that large tumor size ( > 20 mm), higher grade, PR –, and unfavorable histology were independent risk factors for higher RS in patients with localized early stage HR+/HER2+. High RS was associated with worse outcome.

scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

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.

scholarly journals Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition

2020 ◽  
Vol 6 (25) ◽  
pp. eabb2210 ◽  
Author(s):  
Anne Fassl ◽  
Christopher Brain ◽  
Monther Abu-Remaileh ◽  
Iga Stukan ◽  
Deborah Butter ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Breast Cancers ◽  
Cyclin Dependent Kinases ◽  
Hormone Receptor Positive ◽  
Inhibitor Compounds ◽  
Resistant Cells

Inhibitors of cyclin-dependent kinases CDK4 and CDK6 have been approved for treatment of hormone receptor–positive breast cancers. In contrast, triple-negative breast cancers (TNBCs) are resistant to CDK4/6 inhibition. Here, we demonstrate that a subset of TNBC critically requires CDK4/6 for proliferation, and yet, these TNBC are resistant to CDK4/6 inhibition due to sequestration of CDK4/6 inhibitors into tumor cell lysosomes. This sequestration is caused by enhanced lysosomal biogenesis and increased lysosomal numbers in TNBC cells. We developed new CDK4/6 inhibitor compounds that evade the lysosomal sequestration and are efficacious against resistant TNBC. We also show that coadministration of lysosomotropic or lysosome-destabilizing compounds (an antibiotic azithromycin, an antidepressant siramesine, an antimalaria compound chloroquine) renders resistant tumor cells sensitive to currently used CDK4/6 inhibitors. Lastly, coinhibition of CDK2 arrested proliferation of CDK4/6 inhibitor-resistant cells. These observations may extend the use of CDK4/6 inhibitors to TNBCs that are refractory to current anti-CDK4/6 therapies.

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