A cross-sectional study on the pattern of recurrence in carcinoma breast patients based on molecular subtypes

Background: Breast cancer is a major public health issue and it is the leading cause of cancer related death in females worldwide. New insights in the cancer treatment led to considerable improvement in the survival of cancer patients. But metastasis remain an area were all sorts of conventional treatments fails and it is the cause of death of most carcinoma breast patients. In this study we aim to establish a possible link to local recurrence and distant metastasis with different biological subtypes of breast cancer.Methods: One hundred and eighty patients of carcinoma breast patients of carcinoma breast who presented with local recurrence or distant metastasis in the period of January 2018 to March 2019 in Government Medical College, Thiruvananthapuram were included in this study. These data were collected from the hospital records.Results: Local recurrence was most seen in triple negative (50%) subtype followed by HER2 (32.1%) enriched. Local recurrence was least among luminal A (13.8%) with a p value of 0.001. Bone metastasis was the most common type of metastasis and was most seen in luminal A (p=0.001). Triple negative had the maximum CNS metastasis with a p value of 0.003. Liver metastasis was seen mostly in luminal B (26.2%) and A (20.7%) and lung metastasis in triple negative (13.5%) and HER2/neu (10.7%). However, there was no significant association for lung or liver metastasis to any subtype.Conclusions: Biological subtypes of breast cancer classified by immunohistochemical expression of ER, PR, HER2, Ki 67 show different clinicopathological features, recurrence pattern, and survival outcomes.

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Expression of Kl67 In ER+ PR+ HER2- & ERr- PRr- HER2- Breast Cancer Patients

Journal of Surgical Sciences ◽

10.3329/jss.v20i2.43812 ◽

2019 ◽

Vol 20 (2) ◽

pp. 37-41

Author(s):

Md Hasanuzzaman ◽

Md Johirul Lslam ◽

AZM Mostaque Hossain ◽

Md Rassell ◽

Md Mafizur Rahman ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Duct Cell ◽

Surgical Oncology ◽

P Value ◽

Breast Cancer Patients ◽

Luminal A ◽

Ki 67 ◽

Her2 Breast Cancer

Background: Carcinoma of the breast is one of the most common malignancies in women worldwide. Objective: The current study was conducted to evaluate the role of Ki-67 as a prognosticmarker in two definite groups of breast cancer patients (ER+ve, PR+ve, HER-ve& triple negative)in Bangladesh perspective. Methods: Sixty nine female breast cancer patients operated at the surgical oncology departmentof National Institute of Cancer Research & Hospital were selected by non-probabilitysampling method and operated specimens were sent for immunohistochemical study of theER, PR, Her2/neu receptors and Ki-67 protein analysis. Statistical analysis was conductedusing SPSS version 17 for Windows software. P-value 0.05 or less was considered as significant. Result: The mean age of the patients was 46.96 years with SD of± 13.13 years. Histopathologyreports revealed that 94.2% (65/69) were suffering from duct cell carcinoma (DCC) whilelobular varieties were found in 2 cases. Majority of the patients with ER+, PR+ and Ki-67 +vestatus were between 36-50 years of age. But for Her2/neu positive cases most of patientswere above 50 years of age. In Luminal A category cancer patients 69.7% showed positiveKi-67 expression but in case of triple negative cases this percentage was 87.5%. However, thisdifference was not statistically significant. Conclusion: Scores based upon staining of ER, PR, Her2/neu and Ki-67 collectively known asIHC4 which can be used as prognostic markers in breast cancer patients. Journal of Surgical Sciences (2016) Vol. 20 (2) :37-41

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Apparent diffusion coefficient cannot predict molecular subtype and lymph node metastases in invasive breast cancer: a multicenter analysis

BMC Cancer ◽

10.1186/s12885-019-6298-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Alexey Surov ◽

Yun-Woo Chang ◽

Lihua Li ◽

Laura Martincich ◽

Savannah C. Partridge ◽

...

Keyword(s):

Breast Cancer ◽

Diffusion Coefficient ◽

Triple Negative ◽

Molecular Subtype ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Apparent Diffusion ◽

Adc Values ◽

Her 2

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.

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Age, Breast Cancer Subtype Approximation, and Local Recurrence After Breast-Conserving Therapy

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.1105 ◽

2011 ◽

Vol 29 (29) ◽

pp. 3885-3891 ◽

Cited By ~ 255

Author(s):

Nils D. Arvold ◽

Alphonse G. Taghian ◽

Andrzej Niemierko ◽

Rita F. Abi Raad ◽

Meera Sreedhara ◽

...

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Systemic Therapy ◽

Cumulative Incidence ◽

Triple Negative ◽

Multivariable Analysis ◽

Breast Conserving Therapy ◽

Luminal A ◽

Her2 Positive ◽

Luminal B

Purpose Prior results of breast-conserving therapy (BCT) have shown substantial rates of local recurrence (LR) in young patients with breast cancer (BC). Patients and Methods We studied 1,434 consecutive patients with invasive BC who received BCT from December 1997 to July 2006. Ninety-one percent received adjuvant systemic therapy; no patients received trastuzumab. Five BC subtypes were approximated: estrogen receptor (ER) or progesterone receptor (PR) positive, HER2 negative, and grades 1 to 2 (ie, luminal A); ER positive or PR positive, HER2 negative, and grade 3 (ie, luminal B); ER or PR positive, and HER2 positive (ie, luminal HER2); ER negative, PR negative, and HER2 positive (ie, HER2); and ER negative, PR negative, and HER2 negative (ie, triple negative). Actuarial rates of LR were calculated by using the Kaplan-Meier method. Results Median follow-up was 85 months. Overall 5-year cumulative incidence of LR was 2.1% (95% CI, 1.4% to 3.0%). The 5-year cumulative incidence of LR was 5.0% (95% CI, 3.0% to 8.3%) for age quartile 23 to 46 years; 2.2% (95% CI, 1.0% to 4.6%) for ages 47 to 54 years; 0.9% (95% CI, 0.3% to 2.6%) for ages 55 to 63 years; and 0.6% (95% CI, 0.1% to 2.2%) for ages 64 to 88 years. The 5-year cumulative incidence of LR was 0.8% (95% CI, 0.4% to 1.8%) for luminal A; 2.3% (95% CI, 0.8% to 5.9%) for luminal B; 1.1% (95% CI, 0.2% 7.4%) for luminal HER2; 10.8% (95% CI, 4.6% to 24.4%) for HER2; and 6.7% (95% CI, 3.6% to 12.2%) for triple negative. On multivariable analysis, increasing age was associated with decreased risk of LR (adjusted hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = .009). Conclusion In the era of systemic therapy and BC subtyping, age remains an independent prognostic factor after BCT. However, the risk of LR for young women appears acceptably low.

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ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s10701 ◽

2013 ◽

Vol 7 ◽

pp. BCBCR.S10701 ◽

Cited By ~ 10

Author(s):

Kristiina Joensuu ◽

Marjut Leidenius ◽

Mia Kero ◽

Leif C. Andersson ◽

Kathryn B. Horwitz ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Triple Negative ◽

Significant Risk ◽

Growth Factor Receptor ◽

Primary Therapy ◽

Breast Cancers ◽

Luminal A ◽

Ki 67 ◽

Luminal B

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.

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Comparison of diagnostic validity between mitotic activity index and Ki-67 expression as predictor for breast cancer in distant metastasis

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20192154 ◽

2019 ◽

Vol 7 (6) ◽

pp. 2072

Author(s):

Andreasta Ginting ◽

I. Gede Budhi Setiawan ◽

I. Wayan Sudarsa ◽

I. Gede Raka Widiana

Keyword(s):

Breast Cancer ◽

Mitotic Activity ◽

Distant Metastasis ◽

Activity Index ◽

P Value ◽

Breast Cancer Patients ◽

Ki 67 ◽

Diagnostic Characteristics ◽

Significant Difference ◽

Mitotic Activity Index

Background: One particular cause of death from breast cancer is distant metastasis. In this study, we calculate and compare diagnostic value of Mitotic Activity Index (MAI) and Ki-67 expression in predicting distant metastasis.Methods: Study was conducted in Sanglah Hospital from January 2017 to February 2019. All histopathology results from open biopsy are examined, thus MAI and Ki-67 values were obtained. We divided this into 2 groups: MAI high (≥20/HPF), low (<20/HPF) and Ki-67 high (≥20%) and low (<20%). We compared with distant metastasis event as gold standard, obtained from radiology examination. We count all diagnostic characteristics (sensitivity, specificity, positive and negative predictive value, accuracy, and likelihood ratio). We compared these diagnostic validities from data area under curve (AUC) with p value <0.005 considered to be statistically significant.Results: A total of 173 breast cancer patients were participated in this study, 92 of them had distant metastasis (53.2%) and 81 patients didn’t have any distant metastasis (46.8%). MAI had relative high specificity (82.7%) and Ki-67 had fair sensitivity values (69.6%). There are 0.08 point AUC differences between these two variables. With p value higher than 0.05 (0.06), it can be summarized that these two variables are not different significantly and statistically.Conclusions: There is not any statistically significant difference between these two markers in predicting distant metastasis in breast cancer. We hope other researcher interest into exploring more about these markers and their function.

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Molecular profiling of breast carcinoma with IHC surrogates in a tertiary care centre in South India

Biomedicine ◽

10.51248/.v41i1.537 ◽

2021 ◽

Vol 41 (1) ◽

pp. 75-81

Author(s):

N. Priyathersini ◽

J. Thanka ◽

B Jayashree

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Triple Negative ◽

Ductal Carcinoma ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Tertiary Care ◽

P Value ◽

Her2 Receptor ◽

Luminal A

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years. Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status. Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors. Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.

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Poor Biological Factors and Prognosis of Interval Breast Cancers: Long-Term Results of Bahçeşehir (Istanbul) Breast Cancer Screening Project in Turkey

JCO Global Oncology ◽

10.1200/go.20.00145 ◽

2020 ◽

pp. 1103-1113

Author(s):

Neslihan Cabioğlu ◽

Sibel Özkan Gürdal ◽

Arda Kayhan ◽

Nilüfer Özaydın ◽

Cennet Şahin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Screening ◽

Breast Cancer Screening ◽

Triple Negative ◽

Long Term Results ◽

Breast Cancers ◽

Interval Cancers ◽

Luminal A ◽

Ki 67 ◽

Luminal B

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.

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Disease-free Probability and Triple-Negative Breast Cancer

Ramathibodi Medical Journal ◽

10.33165/rmj.2012.35.1.117663 ◽

2012 ◽

Vol 35 (1) ◽

pp. 5-13

Author(s):

Prakasit Chirappapha ◽

Thongchai Sukarayothin ◽

Yodying Wasuthit ◽

Ronnarat Suvikapalornkul ◽

Panuwat Lertsithichai ◽

...

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Triple Negative Breast Cancer ◽

Distant Metastasis ◽

Triple Negative ◽

Free Probability ◽

Growth Factor Receptor ◽

Tumor Stage ◽

Breast Cancers ◽

Breast Cancer Patients

Objective: To compare the probabilities of local recurrence and distant metastasis between women with triple-negative and non- triple negative breast cancers. Methods: Medical and pathological records of breast cancer patients treated between the years 2002 and 2006 were reviewed. Results: There were 256 patients with complete data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression determinations. There were 54 patients (21%) with triple-negative (ER-, PR-, HER2 -) cancers. Triple-negative patients were more likely to have larger tumors with higher histologic grade. The median fallow-up time was 4 years. The probabilities of local and distant recurrence were similar between the two groups of patients. Only two factors were independently and significantly associated with overall recurrence: tumor stage and tumor size. Conclusion: Triple-negative breast cancer did not have a higher risk for both local recurrence and distant metastasis when compared with non-triple negative cancer.

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Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer

Breast Disease ◽

10.3233/bd-219004 ◽

2021 ◽

pp. 1-5

Author(s):

M. Husni Cangara ◽

Upik A. Miskad ◽

Rina Masadah ◽

Berti J. Nelwan ◽

Syarifuddin Wahid

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Receptor Expression ◽

Luminal A ◽

Ki 67 ◽

Her 2 ◽

Hormone Receptor Expression

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

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