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      Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients

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          Abstract

          Background

          Prognosis of breast cancer and success of therapeutic interventions largely rely on the clinico-pathologic and biological characteristics of the tumor and vary due to the heterogeneous nature of breast cancers. The aim of this study was to determine the frequency and prognostic parameters of luminal breast cancers in our population to devise targeted and personalized therapeutic regimens tailored to the needs of the loco-regional population.

          Methods

          A retrospective cross-sectional study including 1951 cases of primary breast cancer treated at Liaquat National Hospital Karachi was conducted during the year 2011–2016. The clinico-pathologic characteristics were observed and semiquantitative immunohistochemical analysis was performed to study the luminal subtypes A and B. The cross-tabulated statistics of the observed characteristics were performed between the two subtypes. The significance level of each characteristic was estimated utilizing the chi-square test.

          Results

          Luminal cancers comprised 62.7% of the total number of cases diagnosed with breast cancers in the study period. Out of these 1224 cases of luminal cancers, 845 cases (69%) were luminal B, while 379 (31%) cases were of luminal A. Luminal B cancers were significantly more common in younger age groups as compared to luminal A cancers. Comparison of the two subtypes of luminal breast cancers revealed significant differences. Luminal B cancers were associated with higher grade (26% grade III in luminal B compared to 8% in luminal A), micropapillary histology, and high frequency of nodal metastasis (54 vs. 43%).

          Conclusions

          Luminal B comprised the most frequent subtype of breast cancer in our study and they were found more constantly in a younger age group. Moreover, they were associated with adverse clinico-histologic parameters like higher grade and nodal metastasis. Therefore, we suggest that, despite lack of widespread availability of molecular studies in our setup, IHC-based typing should be done in every case of breast cancer to individualize therapy.

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          Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer

          Maggie C. U. Cheang, Stephen Chia, David Voduc … (2009)
          Background Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression. Results Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes. Conclusion Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.
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            Concordance among gene-expression-based predictors for breast cancer.

            Cheng Fan, Daniel S Oh, Lodewyk F.A. Wessels … (2006)
            Gene-expression-profiling studies of primary breast tumors performed by different laboratories have resulted in the identification of a number of distinct prognostic profiles, or gene sets, with little overlap in terms of gene identity. To compare the predictions derived from these gene sets for individual samples, we obtained a single data set of 295 samples and applied five gene-expression-based models: intrinsic subtypes, 70-gene profile, wound response, recurrence score, and the two-gene ratio (for patients who had been treated with tamoxifen). We found that most models had high rates of concordance in their outcome predictions for the individual samples. In particular, almost all tumors identified as having an intrinsic subtype of basal-like, HER2-positive and estrogen-receptor-negative, or luminal B (associated with a poor prognosis) were also classified as having a poor 70-gene profile, activated wound response, and high recurrence score. The 70-gene and recurrence-score models, which are beginning to be used in the clinical setting, showed 77 to 81 percent agreement in outcome classification. Even though different gene sets were used for prognostication in patients with breast cancer, four of the five tested showed significant agreement in the outcome predictions for individual patients and are probably tracking a common set of biologic phenotypes. Copyright 2006 Massachusetts Medical Society.
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              Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.

              Aleix Prat, Maggie Cheang, Miguel Martín … (2013)
              Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%.
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                Author and article information

                Contributors
                Atif Ali Hashmi: doc_atif2005@yahoo.com
                Saher Aijaz: saheraijaz@gmail.com
                Saadia Mehmood Khan: smk.state.alchemist@gmail.com
                Raeesa Mahboob: raeesaalam18@gmail.com
                Muhammad Irfan: irfan.zafar@lnh.edu.pk
                Narisa Iftikhar Zafar: narisa_iftikhar@hotmail.com
                Mariam Nisar: bluedevil_mn@hotmail.com
                Maham Siddiqui: mahamsidiqui@gmail.com
                Muhammad Muzzammil Edhi: Muhammad_edhi@brown.edu
                Naveen Faridi: Naveen.faridi@lnh.edu.pk
                Amir Khan:
                ORCID: http://orcid.org/0000-0002-8763-7690
                dramirkhan04@gmail.com
                Journal
                Journal ID (nlm-ta): World J Surg Oncol
                Journal ID (iso-abbrev): World J Surg Oncol
                Title: World Journal of Surgical Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-7819
                Publication date (Electronic): 2 January 2018
                Publication date PMC-release: 2 January 2018
                Publication date Collection: 2018
                Volume: 16
                Electronic Location Identifier: 1
                Affiliations
                [1 ]ISNI 0000 0004 0637 9066, GRID grid.415915.d, Liaquat National Hospital and Medical College, ; Karachi, Pakistan
                [2 ]GRID grid.444886.2, Shaheed Zulfiqar Ali Bhutto Institute of Science and Technology, ; Karachi, Pakistan
                [3 ]ISNI 0000 0001 0633 6224, GRID grid.7147.5, Aga Khan University, ; Karachi, Pakistan
                [4 ]ISNI 0000 0004 0637 9066, GRID grid.415915.d, Department of Pathology, , Liaquat National Hospital and Medical College, ; Karachi, Pakistan
                [5 ]ISNI 0000 0004 1936 9094, GRID grid.40263.33, Department of Surgery, , Brown University, ; Providence, RI USA
                [6 ]GRID grid.440459.8, Department of Medicine, , Kandahar University, ; Kandahar, Afghanistan
                Author information
                http://orcid.org/0000-0002-8763-7690
                Article
                Publisher ID: 1299
                DOI: 10.1186/s12957-017-1299-9
                PMC ID: 5749004
                PubMed ID: 29291744
                SO-VID: 4dd49f32-bcf6-421d-9c76-d3d15cc97ea3
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 15 August 2017
                Date accepted : 18 December 2017
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Surgery
                Keywords: luminal a,luminal b,er,pr,her2neu,breast cancer
                Data availability:
                ScienceOpen disciplines: Surgery
                Keywords: luminal a, luminal b, er, pr, her2neu, breast cancer

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