• Title, Summary, Keyword: Breast cancer subtype

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Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer Characteristics and Method of Detection

  • Chu, A Jung;Chang, Jung Min;Cho, Nariya;Moon, Woo Kyung
    • Journal of Breast Cancer
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    • v.20 no.2
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    • pp.192-197
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    • 2017
  • Purpose: The aim of our study was to investigate the characteristics of primary and recurrent breast cancers and the correlation between cancer subtypes and detection modes. Methods: Between 2003 and 2013, 147 cases of recurrent breast cancer in 137 women (mean age, $45.30{\pm}10.78years$) were identified via an annual clinical examination using radiological studies among 6,169 patients with a breast cancer history (mean followup period, $13.26{\pm}1.78years$). Clinical, radiological, and pathological findings including immunohistochemistry findings of primary and recurrent cancers were reviewed. The size of the tumor in primary and recurrent cancers, disease-free survival, methods of surgery, and the recurrence detection modalities were analyzed with respect to the breast cancer subtype. Results: Ipsilateral and contralateral in-breast recurrence occurred in 105, 21 had axillary lymph node recurrence, and 21 had chest wall recurrences. The subtypes of the primary cancers were hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative (HR+HER2-) in 57, HER2 positive (HER2+) in 39, and triple-negative type in 51, and the recurrent cancers in each subtype showed the same type as the primary cancer in 84.3% of cases. In the in-breast recurrent cancers, the HR+HER2- cancers were most frequently detected using ultra-sonography (15/43) followed by mammography (MG) (11/43). The HER2+ recurrent cancers were most commonly detected using MG (14/31, 45.2%), whereas triple-negative type recurrent cancers most commonly presented as symptomatic masses (15/31) (p=0.028). Conclusion: Most recurrent breast cancers showed the same cancer subtype as the primary tumor, and recurrent breast cancer subtypes correlated with the detection modality. Imaging surveillance of survivors of breast cancer might be more beneficial in cases of HR+HER2- type breast cancer or HER2+ type breast cancer than in cases of triple-negative type breast cancer.

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

  • Temian, Daiana Cosmina;Pop, Laura Ancuta;Irimie, Alexandra Iulia;Berindan-Neagoe, Ioana
    • Journal of Breast Cancer
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    • v.21 no.3
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    • pp.233-243
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    • 2018
  • Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies - the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis - DNA methylation, histone modifications, and noncoding RNAs - advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Breast Cancer Molecular Subtypes and Associations with Clinicopathological Characteristics in Iranian Women, 2002-2011

  • Kadivar, Maryam;Mafi, Negar;Joulaee, Azadeh;Shamshiri, Ahmad;Hosseini, Niloufar
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1881-1886
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    • 2012
  • Breast cancer is a heterogeneous disease that is affected by ethnicity of patients. According to hormone receptor status and gene expression profiling, breast cancers are classified into four molecular subtypes, each showing distinct clinical behavior. Lack of sufficient data on molecular subtypes of breast cancer in Iran, prompted us to investigate the prevalence and the clinicopathological features of each subtype among Iranian women. A total of 428 women diagnosed with breast cancer from 2002 to 2011 were included and categorized into four molecular subtypes using immunohistochemistry. Prevalence of each subtype and its association with patients' demographics and tumor characteristics, such as size, grade, lymph-node involvement and vascular invasion, were investigated using Chi-square, analysis of variance and multivariate logistic regression. Luminal A was the most common molecular subtype (63.8%) followed by Luminal B (8.4%), basal-like (15.9%) and HER-2 (11.9%). Basal-like and HER-2 subtypes were mostly of higher grades while luminal A tumors were more of grade 1 (P<0.001). Vascular invasion was more prevalent in HER-2 subtype, and HER-2 positive tumors were significantly associated with vascular invasion (P=0.013). Using muti-variate analysis, tumor size greater than 5 cm and vascular invasion were significant predictors of 3 or more nodal metastases. Breast cancer was most commonly diagnosed in women around 50 years of age and the majority of patients had lymph node metastasis at the time of diagnosis. This points to the necessity for devising an efficient screening program for breast cancer in Iran. Further, prospective surveys are suggested to evaluate prognosis of different subtypes in Iranian patients.

Overweight, Obesity, Oxidative Stress and the Risk of Breast Cancer

  • Kruk, Joanna
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9579-9586
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    • 2014
  • There is growing scientific evidence linking excess body weight to breast cancer risk. However, there is no common consensus on this relation due partly to methodologies used, populations studied and the cancer subtype. We report here a summary of the present state of knowledge on the role of overweight and obesity in pathogenesis of breast cancer and possible mechanisms through which excess body weight might influence the risk, focusing on the role of oxidative stress in breast cancer etiology. The findings demonstrate duality of excess body weight action in dependence on menopausal status: a statistically significant increased risk in postmenopausal overweight/ obese women and non-significant preventive effect among premenopausal women. Due to several gaps in the literature on this topic, additional studies are needed. Future research should address factors influencing the excess body weight - breast cancer relationship, such as race/ethnicity, tumor subtype, receptor status, the most appropriate measure of adiposity, reproductive characteristics, and lifestyle components.

Survival of Triple Negative versus Triple Positive Breast Cancers: Comparison and Contrast

  • Negi, Preety;Kingsley, Pamela Alice;Jain, Kunal;Sachdeva, Jaineet;Srivastava, Himanshu;Marcus, Sudeep;Pannu, Aman
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3911-3916
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    • 2016
  • Background: Triple negative (TN) and triple positive (TP) breast cancers both are aggressive types but TN generally has a shorter survival. Objectives: To compare the clinical characteristics and treatment outcomes for patients with TN versus TP breast cancer and to assess various prognostic factors affecting overall survival. Materials and Methods: A retrospective audit of 85 breast cancer patients was conducted in the Department of Radiation Oncology and Medical Oncology on patients from 2006 to 2013 for whom IHC for ER, PgR and Her-2 neu were available. The patients were stratified into: ER-, PR- and Her-2 neu- (Arm A, n=47) and ER+, PgR+ and Her-2 neu+ (Arm B, n=38). Results: TN subtype had higher numbers of premenopausal and advanced stage patients as compared to TP subtype. The locoregional recurrence (LRR) and distant metastatic rate was also higher in TN subtype but there was no definite pattern in both the arms. Among the prognostic factors, patients with premenopausal status and advanced stage in TN breast cancer had inferior survival (P=0.07) whereas for those with postmenopausal status and early stage there was no survival difference between the two arms. Conclusions: TN subtype tends to be more aggressive in terms of younger age and advanced stage at presentation, higher tumour grade, LRR and metastasis, suggesting need for future research efforts on providing aggressive treatment to these patients. We could attribute better outcome for TP subtype to receptor positivity enabling role of hormonal treatment and targeted therapy, although less number of patients received targeted therapy.

Clinicopathological Features of Indonesian Breast Cancers with Different Molecular Subtypes

  • Widodo, Irianiwati;Dwianingsih, Ery Kus;Triningsih, Ediati;Utoro, Totok;Soeripto, Soeripto
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6109-6113
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    • 2014
  • Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

Angiogenesis Markers in Breast Cancer - Potentially Useful Tools for Priority Setting of Anti-Angiogenic Agents

  • Keyhani, Elahe;Muhammadnejad, Ahad;Behjati, Farkhondeh;Sirati, Fereidoon;Khodadadi, Faranak;Karimlou, Masoud;Moghaddam, Fatemeh A.;Pazhoomand, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7651-7656
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    • 2013
  • Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

Assessment of Ki-67 for Predicting Effective Prognosis in Breast Cancer Subtypes

  • Park, Sangjung;Park, Sunyoung;Kim, Jungho;Ahn, Sungwoo;Park, Kwang Hwa;Lee, Hyeyoung
    • Biomedical Science Letters
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    • v.24 no.1
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    • pp.9-14
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    • 2018
  • Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

Clinical Differences in Triple-Positive Operable Breast Cancer Subtypes in Korean Patients: An Analysis of Korean Breast Cancer Registry Data

  • You, Sun Hyong;Chae, Byung Joo;Eom, Yong Hwa;Yoo, Tae-Kyung;Kim, Yong-seok;Kim, Jeong Soo;Park, Woo-Chan
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.415-424
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    • 2018
  • Purpose: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. Methods: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. Results: KBCS registry data (2006-2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p<0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p<0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p<0.001). Conclusion: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

  • Hwang, Ki-Tae;Han, Wonshik;Kim, Jongjin;Moon, Hyeong-Gon;Oh, Sohee;Song, Yun Seon;Kim, Young A;Chang, Mee Soo;Noh, Dong-Young
    • Journal of Breast Cancer
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    • v.20 no.1
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    • pp.54-64
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    • 2017
  • Purpose: We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. Methods: We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results: Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(-) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(-)/HER2(+) and HR(-)/HER2(-) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(-) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(-), HR(+)/HER2(+), and HR(-)/HER2(-) subtypes, but not in HR(-)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. Conclusion: The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(-) or luminal A and luminal B/HER2(-) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.