Is Molecular Subtype of Breast Cancer has an Impact on Risk of Relapse and Type of Adjuvant Chemotherapy: A Retrospective Study

Ayman Abd Elsalam Mahmoud


Breast cancer is the most frequently diagnosed malignancy, accounting for over a million cases each year. It is also the leading cause of cancer death in women worldwide. the second most common cause of cancer death in women after lung cancer, and the main cause of death in women ages 20 to 59 years. (Siegel R et al., 2013). Breast cancer is the most common cancer among women in Egypt. The proportion of breast cancer among Egyptian females was 32.0% followed by liver cancer 13.5 %.(Amal S et al., 2014). Major risk factors for breast cancer in women are age, genetic predisposition, and estrogen exposure. Breast density is also a significant risk factor; particularly in women aged 40 to 49 years (Nelson H et al. 2012). A variety of imaging modalities, as well as clinical breast examination and breast self-examination, have been developed for breast cancer screening. Mammography remains the mainstay of screening for breast cancer, with multiple randomized trials finding it decreases breast cancer mortality. Ultrasonography is commonly used for diagnostic follow-up of an abnormality seen on screening mammography, to clarify features of a potential lesion. The role of magnetic resonance imaging (MRI) for breast cancer screening is emerging; currently MRI screening, in combination with mammography, is targeted to high-risk patients. Newer tests are under evaluation (Drukteinis J et al., 2013). The widespread application of adjuvant systemic therapy has reduced mortality from breast cancer in the Western world (Peto R et al., 2012). Unfortunately, many patients are not treated appropriately, with some overtreated and others undertreated. It would be of great value to have reliable prognostic factors that could help select those patients most at risk for recurrence (Forouzanfar M et al. 2011). For women with newly diagnosed non-metastatic breast cancer, routinely the following clinical factors utilized to help determine prognosis, Age, Pathologic factors, including tumor stage And Tissue markers, including hormone receptor expression and human epidermal growth factor 2 (HER2) overexpression (Isabelle S et al., 2008). Breast cancer is no longer considered a single entity but is instead a heterogeneous disease composed of distinct biological and phenotypical subtypes with diverse clinical, pathological, molecular, and genetic features and different therapeutic responsiveness and outcomes (Spitale A et al. 2009). Gene expression studies have identified several distinct breast cancer subtypes that differ markedly in prognosis and in the therapeutic targets they express. The list of genes that differentiates these subtypes is called the intrinsic list and is made up of several clusters of genes relating to estrogen receptor (ER) expression (the luminal cluster), human epidermal growth factor 2 (HER2) expression, proliferation, and a unique cluster of genes called the basal cluster (Prat A et al., 2010). In an effort to identify an alternative to gene expression analysis for defining intrinsic breast cancer subtypes, an immunohistochemistry assay of four standard markers (ER, PR, HER2, and Ki67) was developed, known as the IHC4. Some studies show it can effectively separate luminal A from luminal B tumors (Cheang M et al. 2009) and has a similar prognostic profile as the 21-gene recurrence score assay (Cuzick J et al. 2011). The panel at the recent St Gallen Consensus Conference accepted the principle of using intrinsic tumor subtype as a basis for identifying patients for whom each type of therapy is most likely to be beneficial and, conversely, those for whom a particular treatment may be futile. (Coates A et al. 2015). This study is a retrospective analysis of the distribution of molecular subtypes of breast cancer using IHC markers among breast cancer patients at the Clinical Oncology Department, Ain Shams University. The current study included 329 female with stage I to stage III breast cancer diagnosed between January 2012 and December 2014. The median age was 44 years (range, 23 – 65 years) and the median follow up period was 26 months (range, 8 – 44 months). In this study, different correlations were done between molecular subtypes of breast cancer and clinicopathological factors. Also risk of relapse was correlated with different clinicopathological factors, molecular subtypes of breast cancer and different modalities of treatment. The most common age group in this study was 40-55 years (48.32%). The most common pathological subtype was IDC (93%) and the most common histological grade was grade II (92.4%). Stage III was the most prevalent in this study (48.32%). Molecular subtypes were determined and luminal A was the most prevalent followed by luminal B, triple negative and HER2 enriched. There was statistically significant correlation between molecular subtypes and age at diagnosis, pathological subtypes and tumor grade. Conversely, correlations of molecular subtypes with tumor size, lymph node status and tumor stage were not significant. Family history of breast cancer was correlated with different age groups. It was noticed that patients with positive family history of breast cancer had a tendency to present at younger ages. Also, family history correlated with tumor stage. Stage III was more common in patients with positive family history. Tumor size has an important prognostic role and the incidence of lymph node metastasis was obviously increasing along with increasing tumor size. The risk of relapse was correlated with different clinicopathological factors. Regarding age at diagnosis, the risk of relapse was high in younger patients and low in older patients. The risk of relapse was increased gradually with increasing tumor size and number of axillary lymph node metastasis. Also the risk of relapse was correlated with molecular subtypes of breast cancer. Luminal A had the lowest risk of relapse while HER2 enriched had the highest risk of relapse. In this study luminal A associated with low rate of local and distant metastasis while HER2 enriched associated with high rate of local and distant metastasis. This study also demonstrated that breast cancer subtypes were associated with unique patterns of metastatic spread. Luminal A and luminal B subtypes showed high proportion of bone and liver metastasis. HER2 enriched subtype had high proportion of brain metastasis while triple negative was associated with high proportion of lung metastasis.

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Other Titles هل الأنواع الجزيئية لورم الثدى لها تأثير على خطورة الأرتجاع ونوع العلاج الكيمائى: دراسة استرجاعية
Issue Date 2016

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