Metaplastic breast cancer: Prognostic and therapeutic considerations.

INTRODUCTION: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. METHODS: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). RESULTS: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. CONCLUSION: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis.

BACKGROUND: Oncoplastic surgery is a well-established approach that combines conserving treatment for breast cancer and plastic surgery techniques. Although this approach has been described for T2 tumors, no long-term oncologic follow-up and no comparison with patients undergoing mastectomy has been published. The purpose of the study was to demonstrate that oncoplastic surgery is a safe and reliable treatment for managing invasive primary T2 breast cancer. METHODS: We compared a consecutive series of 193 T2 patients who have undergone oncoplastic surgery (study group) with 386 T2 patients who have undergone mastectomy (control group). The endpoints evaluated were disease-free survival (DFS), overall survival (OS), cumulative incidence of local recurrence (CI-L), regional recurrence (CI-R), and distant recurrence (CI-D), all measured from the date of surgery. RESULTS: Median follow-up is 7.4 years. The OS is similar within the two groups: 87.3 and 87.1 % at 10 years in the ONC group and control group, respectively (p value, adjusted for multifocality and tumor size, 0.74). Also, the DFS is similar in both groups: 60.9 and 56.3 % at 10 years in the ONC group and control group, respectively. The incidence of local events is slightly higher in the oncoplastic group, whereas the incidence of regional events is slightly higher in the mastectomy group. These differences are not statistically significant. The cumulative incidence of distant events is similar within the two groups. CONCLUSIONS: To our knowledge, the present study provides the best available evidence to suggest that oncoplastic approach is a safe and reliable treatment for managing invasive pT2 breast cancers.

Targeting bone metastatic cancer: Role of the mTOR pathway.

One of the great challenges of cancer medicine is to develop effective treatments for bone metastatic cancer. Most patients with advanced solid tumors will develop bone metastasis and will suffer from skeletal related events associated with this disease. Although some therapies are available to manage symptoms derived from bone metastases, an effective treatment has not been developed yet. The mammalian target of rapamycin (mTOR) pathway regulates cell growth and survival. Alterations in mTOR signaling have been associated with pathological malignancies, including bone metastatic cancer. Inhibition of mTOR signaling might therefore be a promising alternative for bone metastatic cancer management. This review summarizes the current knowledge on mTOR pathway signaling in bone tissue and provides an overview on the known effects of mTOR inhibition in bone cancer, both in in vitro and in vivo models.

The added value of whole-body magnetic resonance imaging in the management of patients with advanced breast cancer.

This study investigates the impact of whole-body MRI (WB-MRI) in addition to CT of chest-abdomen-pelvis (CT-CAP) and 18F-FDG PET/CT (PET/CT) on systemic treatment decisions in standard clinical practice for patients with advanced breast cancer (ABC). WB-MRI examinations in ABC patients were extracted from our WB-MRI registry (2009-2017). Patients under systemic treatment who underwent WB-MRI and a control examination (CT-CAP or PET/CT) were included. Data regarding progressive disease (PD) reported either on WB-MRI or on the control examinations were collected. Data regarding eventual change in treatment after the imaging evaluation were collected. It was finally evaluated whether the detection of PD by any of the two modalities had induced a change in treatment. Among 910 WB-MRI examinations in ABC patients, 58 had a paired control examination (16 CT-CAP and 42 PET/CT) and were analysed. In 23/58 paired examinations, additional sites of disease were reported only on WB-MRI and not on the control examination. In 17/28 paired examinations, PD was reported only on WB-MRI and not on the control examination. In 14 out of the 28 pairs of examinations that were followed by a change in treatment, PD had been reported only on WBMRI (14/28; 50%), while stable disease had been reported on the control examination. In conclusion, WB-MRI disclosed PD earlier than the control examination (CT-CAP or PET/CT), and it was responsible alone for 50% of all changes in treatment.

Neoadjuvant therapy in locally advanced breast cancer: 99mTc-MIBI mammoscintigraphy is not a reliable technique to predict therapy response.

Mammoscintigraphy (MMS) has been indicated as a useful tool in predicting response to therapy in cancer. However, contrasting results have been reported in the literature for breast cancer patients. The aim of this study was to explore the role of MMS in locally advanced breast cancer (LABC) patients. Fifty-one patients affected by LABC and scheduled for neoadjuvant therapy were enrolled. Breast tumor status was evaluated at baseline, during therapy and at the completion of therapy by radiological techniques and by MMS. Pre-therapy (MMS1) and post-therapy MIBI (2-methoxyisobutilysonitrile) images (MMS2-3) were analyzed. MMS1 was performed in all pts, 41 carried out MMS2 and 27 had MMS3. Tumor uptake and washout in MMS1 did not show any correlation with the therapy response. The absence of any association between tumor uptake and washout with respect to therapy response suggests that MMS is not a reliable technique to predict therapy response in LABC.

Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer.

Tumor evolution is shaped by many variables, potentially involving external selective pressures induced by therapies. After surgery, patients with estrogen receptor (ERα)-positive breast cancer are treated with adjuvant endocrine therapy, including selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs). However, more than 20% of patients relapse within 10 years and eventually progress to incurable metastatic disease. Here we demonstrate that the choice of therapy has a fundamental influence on the genetic landscape of relapsed diseases. We found that 21.5% of AI-treated, relapsed patients had acquired CYP19A1 (encoding aromatase) amplification (CYP19A1amp). Relapsed patients also developed numerous mutations targeting key breast cancer-associated genes, including ESR1 and CYP19A1. Notably, CYP19A1amp cells also emerged in vitro, but only in AI-resistant models. CYP19A1 amplification caused increased aromatase activity and estrogen-independent ERα binding to target genes, resulting in CYP19A1amp cells showing decreased sensitivity to AI treatment. These data suggest that AI treatment itself selects for acquired CYP19A1amp and promotes local autocrine estrogen signaling in AI-resistant metastatic patients.