scholarly journals Characteristics of HER2-negative breast cancers with FISH-equivocal status according to 2018 ASCO/CAP guideline

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Hui Kong ◽  
Qianming Bai ◽  
Anqi Li ◽  
Xiaoyan Zhou ◽  
Wentao Yang

Abstract Background According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated. Methods 195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0–4.4, 4.5–4.9, 5.0–5.4, 5.5–5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results 183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn’t receive targeted therapy. Conclusions In this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

2021 ◽  
Author(s):  
Hui Kong ◽  
Qianming Bai ◽  
Anqi Li ◽  
Xiaoyan Zhou ◽  
Wentao Yang

Abstract Background: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with HER2 IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods: 195 HER2 FISH-equivocal breast cancers were collected between 2014 and 2018. The molecular subtype was determined according to 2013 St Gallen consensus, and HER2 status was also redefined following 2018 ASCO/CAP guideline. All cases were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results: 183 (93.8%) of 195 FISH-equivocal cases were of luminal subtype, while the other 12 (6.2%) were undetermined. Using 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized to HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) cases were treated with trastuzumab, but showed no difference in prognosis with patients who didn’t receive targeted therapy.Conclusions: In this study, all HER2 FISH-equivocal breast cancers were reclassified to be HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexey Surov ◽  
Yun-Woo Chang ◽  
Lihua Li ◽  
Laura Martincich ◽  
Savannah C. Partridge ◽  
...  

Abstract Background Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. Methods Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. Conclusion ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.


2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii2-ii3
Author(s):  
Maleeha Qazi ◽  
Katarzyna Jerzak ◽  
Sharon Nofech-Mozes

Abstract INTRODUCTION Therapies targeting androgen receptors (AR) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated intracranial activity. In this study, we analyzed the expression of AR and PD-L1 in breast cancer brain metastases (BrM) to identify patients who may benefit from anti-androgenic or anti-PD-1/PD-L1 therapies. METHODS Consecutive BrM resected in our institution (July 1999-June 2013) that were signed out as breast origin were identified and included from the Anatomic Pathology departmental database. A tissue microarray of BrMs was studied by immunohistochemistry for AR, PD-L1, ER, PR and HER2 (SP107, SP142, SP1, IE2, 4B5; Ventana Medical Systems). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (Ventana Medical Systems). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes. RESULTS Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases and PD-L1 was expressed in 9 (15%) cases. Among BrMs of luminal A subtype (ER+PR+/-HER2-Ki67< 16%; n=2), 50% expressed AR and none expressed PD-L1. Within the luminal B subtype (ER+/PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 1 expressed PD-L1 (7%). Among HER2- luminal B subtype BrMs (n=16), 50% and 12.5% of cases expressed AR and PD-L1, respectively. In BrM of HER2+ subtype (ER-/PR-; n=14), 71% expressed AR and 14% expressed PD-L1. The frequency of AR+ (30%) and PD-L1+ (30%) cases was equivalent in triple negative BrM (ER-/PR-/HER2-; n=14). CONCLUSION Almost two-thirds of breast cancer BrM expressed AR, while only 15% expressed PD-L1. HER2+ luminal B and HER2+ subtypes were most likely to be AR+. Meanwhile, PD-L1 expression was predominant in the triple negative subgroup. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ or PD-L1+; intracranial efficacy of AR-antagonists and immunotherapy warrants investigation for breast cancer BrM, particularly in biomarker-positive subtypes.


2021 ◽  
Vol 5 (4) ◽  
pp. 877-881
Author(s):  
Eric Hartoyo Salim ◽  
Eddy Herman Tanggo ◽  
Dwi Hari Susilo

Background. Breast cancer is the highest prevalence of malignancy for women in Indonesia and important national health problem. Estimated 2 million women developed breast cancer in 2018 with a mortality rate of 14.1 in every 100,000 women. Regarding the relationship between subtypes and breast cancer recurrence Several studies on gene expression have shown several subtypes of breast cancer, including the two most important subtypes, estrogen receptor (ER) positive (Luminal A and Luminal B) and ER negative (Triple negative and Her2 positive). Based on the explanation above, currently there is no data in Soetomo Hospital that discusses the role of breast cancer subtypes as a prognostic factor in determining the recurrence rate in locally advanced breast cancer.Methods. The research design is an associative test using a retrospective cohort observational analytical study design, associating the relationship between tumor subtypes with recurrence in locally advanced breast cancer patients after mastectomy and has received additional therapy according to standard procedures at Dr. Soetomo Surabaya This study used secondary data from the medical records of the Oncology Polyclinic, RSUD Dr. Soetomo Surabaya from 2014 to 2019.Results. The research subjects who have been selected according to inclusion criteria are 214 people, with the proportion in the population of luminal A and luminal B subtypes of 107 people each. Based on this study, it was found that the subtype was positively correlated with recurrence in LABC patients who had undergonecmastectomy with a significance value of p = 0.000 (p <0.05; 99% CI).Conclusion. There is a relationship between the recurrence rate and the molecular subtype of breast cancer in locally advanced breast cancer (LABC) patients after mastectomy at Dr Soetomo Hospital.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12571-e12571
Author(s):  
Paula Toro ◽  
Juliana Pava-De Los Rios ◽  
Alex Enrique Pava-Ripoll ◽  
Sebastian Chica ◽  
Edgar Perez ◽  
...  

e12571 Background: Breast cancer is the most common cancer in women and constitutes a public health problem due to its high rates of morbidity and mortality. Diagnosis is made through routine histopathology studies that are complemented by phenotypic expression studies of hormone receptors (estrogen and progesterone receptors), human epidermal growth factor 2 (HER2) and cell proliferation index (Ki67) for their subtyping into molecular groups (luminal A, luminal B, Her2, and triple negative), which have different prognostic and therapeutic implications. Globally, a high prevalence of the Luminal A subtype has been reported, predominantly in North America, Europe, and some Latin American countries; however, the reports in the Colombian population are heterogeneous. The objective of this research is to establish an incidence profile of these molecular subtypes in a population of the coffee region in Colombia. Methods: Samples of 377 patients with a diagnosis of infiltrating breast cancer were collected retrospectively between 2015 and 2018. Inclusion criteria included: 1) Availability of personal data (year of diagnosis and age) 2) Infiltrating breast carcinoma. 3) Diagnosis between 2015 and 2018. 4) Study of complete immunohistochemistry and/or in situ hybridization (ISH) markers. Results: The histological subtypes included: NOS infiltrating ductal carcinomas (339 cases; 89.9 %), infiltrating lobular (23 cases; 6.1 %), infiltrating mucinous (6 cases; 1.5 %), infiltrating papillary (1 case; 0.2 %) and mixed patterns: ductal - lobular (3 cases; 0.7 %) and mucinous - ductal (5 cases; 1.3 %), of whom 56.2% (212 cases) correspond to luminal B, 22.2% (84 cases) to Luminal A, 14.8% (56 cases) to triple negative and 6.6% (25 cases) to HER2. Conclusions: These findings contrast with the prevalence reported worldwide. Therefore, in the population of the Colombian coffee region, this predominance of the molecular subtype luminal B should be considered when establishing prognosis and treatment plan by the medical staff.


2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii13-ii13
Author(s):  
Maleeha Qazi ◽  
Katarzyna Jerzak ◽  
Sharon Nofech-Mozes

Abstract INTRODUCTION Treatment options for women with breast cancer brain metastases (BrM) are generally limited to surgery and/or radiotherapy because most systemic therapies do not cross the blood-brain barrier. Androgen receptors (ARs) are frequently expressed in breast cancer and anti-androgenic therapies have been shown to penetrate the central nervous system. In this study, we analyzed the expression of AR in breast cancer BrM to identify patients who may benefit from anti-androgenic therapies. METHODS Consecutive BrM resected in our institution (July 1999-June 2013) were identified from the Anatomic Pathology departmental database. Cases that were signed out as breast origin given the available immunohistochemical profile and clinical history were included. A tissue microarray was constructed using 1 mm cores in triplicates and studied by immunohistochemistry for AR, ER, PR and HER2 (SP107, SP1, IE2, 4B5; Ventana Medical Systems, Tucson AZ, USA). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (both by Ventana Medical Systems, Tucson AZ, USA). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes. RESULTS Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases. Among BrMs of luminal A subtype (ER+, PR+/-, HER2-, Ki67&lt;16%), 50% expressed AR (n=1/2). Within the luminal B subtype (ER+, PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 50% of HER2- BrM expressed AR (n=8/16). Among 14 BrM of HER2+ subtype (ER-, PR-), 71% expressed AR (n=10/14). Only 30% of triple negative BrM (ER-, PR-, HER2-) were AR+ (n=4/14). CONCLUSION Almost two-thirds of breast cancer BrM expressed AR. HER2+ luminal B and HER2+ subtypes were most likely to be AR+, while only 30% of triple negative BrM were AR+. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ and could serve as a potential therapeutic target.


2020 ◽  
pp. 1103-1113
Author(s):  
Neslihan Cabioğlu ◽  
Sibel Özkan Gürdal ◽  
Arda Kayhan ◽  
Nilüfer Özaydın ◽  
Cennet Şahin ◽  
...  

PURPOSE The Turkish Bahçeşehir Breast Cancer Screening Project was a 10-year, organized, population-based screening program carried out in Bahçeşehir county, Istanbul. Our aim was to examine the biologic features and outcome of screen-detected and interval breast cancers during the 10-year study period. METHODS Between 2009 and 2019, 2-view mammograms were obtained at 2-year intervals for women aged 40 to 69 years. Clinicopathological characteristics including ER, PR, HER2-neu, and Ki-67 status were analyzed for those diagnosed with breast cancer. RESULTS In 8,758 screened women, 131 breast cancers (1.5%) were detected. The majority of patients (82.3%) had prognostic stage 0-I disease. Contrarily, patients with interval cancers (n = 15; 11.4%) were more likely to have a worse prognostic stage (II-IV disease; odds ratio [OR], 3.59, 95% CI, 0.9 to 14.5) and high Ki-67 scores (OR, 3.14; 95% CI, 0.9 to 11.2). Interval cancers detected within 1 year were more likely to have a luminal B (57.1% v 31.9%) and triple-negative (14.3% v 1%) subtype and less likely to have a luminal A subtype (28.6% v 61.5%; P = .04). Patients with interval cancers had a poor outcome in 10-year disease-specific (DSS) and disease-free survival (DFS) compared with those with screen-detected cancers (DSS: 68.2% v 98.1%, P = .002; DFS: 78.6% v 96.5%, P = .011). CONCLUSION Our findings suggest the majority of screen-detected breast cancers exhibited a luminal A subtype profile with an excellent prognosis. However, interval cancers were more likely to have aggressive subtypes such as luminal B subtype or triple-negative cancers associated with a poor prognosis requiring other preventive strategies.


Sign in / Sign up

Export Citation Format

Share Document