Abstract
Breast cancer is a complex disease, with heterogeneous clinical evolution. Several analyses have been performed to identify the risk factors for breast cancer progression and the patients who respond best to a specific treatment. We aimed to evaluate whether the hormone receptor expression, HER2 and MYC genes and their protein status, and KRAS codon 12 mutations may be prognostic or predictive biomarkers of breast cancer. Protein, gene and mutation status were concomitantly evaluated in 116 breast tumors from women who underwent neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide. We observed that MYC expression was associated with luminal B and HER2 overexpression phenotypes compared to luminal A (p<0.05). The presence of MYC duplication or polysomy 8, as well as KRAS mutation, were also associated with the HER2 overexpression subtype (p<0.05). MYC expression and MYC gain were more frequently observed in early-onset compared to late-onset tumors (p<0.05). KRAS mutation was a risk factor of grade 3 tumors (p<0.05). A multivariate logistic regression demonstrated that MYC amplification defined as MYC/nucleus ratio of ≥2.5 was a protective factor for chemotherapy resistance. On the other hand, age and grade 2 tumors were a risk factor. Additionally, luminal B, HER2 overexpression, and triple-negative tumors presented increased odds of being resistant to chemotherapy relative to luminal A tumors. Thus, breast tumors with KRAS codon 12 mutations seem to present a worse prognosis. Additionally, MYC amplification may help in the identification of tumors that are sensitive to doxorubicin plus cyclophosphamide treatment. If confirmed in a large set of samples, these markers may be useful for clinical stratification and prognosis.
Highlights
Several analyses have been performed to identify the risk factors for breast cancer (BC) progression
We evaluated the hormone receptor (HR) expression, HER2 and MYC genes and their protein status, and KRAS codon 12 mutations in BC from women who underwent neoadjuvant chemotherapy, as well as their associations with clinicopathological features and chemotherapy response
We evaluated ER and PR expression, HER2 and MYC genes and their protein status, and KRAS mutations in the same set of BC
Summary
Several analyses have been performed to identify the risk factors for breast cancer (BC) progression. The histological response to preoperative chemotherapy is one of the most reliable predictors for prognosis of BC patients. Many different chemotherapy regimens have been applied in the preoperative setting. The identification of patients who respond best to a specific treatment is still critical to the appropriate management. Some markers have been described as useful factors for prognostic evaluation or predicting therapeutic response. Several studies demonstrated that lack of estrogen (ER) and/or progesterone (PR) receptors predicts for chemosensitivity [1]. It has been proposed that HER2 (c-erbB2) is a predictor factor for either resistance or sensitivity to different types of chemotherapeutic agents. The literature results are still controversial, especially concerning the response to anthracyclines [2]
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