The Breast : official journal of the European Society of Mastology
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Review
Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway.
Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancers and is a marker of aggressive disease. While HER2-targeted therapies have improved outcomes in these tumors, resistance to these agents develops in a large proportion of patients. ⋯ Several inhibitors of this pathway are under investigation in this disease setting and phase 3 data for everolimus in combination with trastuzumab and chemotherapy in trastuzumab-refractory, advanced disease are promising. In this review, molecular mechanisms underlying resistance to HER2-targeted therapies are considered and evidence for strategies to manage resistance is evaluated, including the use of inhibitors of the PI3K/Akt/mTOR pathway.
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Review Meta Analysis
Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: A systematic meta-analysis comparing breast-conserving surgery versus mastectomy.
Young age is an independent risk factor for local recurrence after breast conserving surgery (BCS) and whole breast radiotherapy (WBRT) for breast cancer. The aim of this study was to carry out a systematic meta-analysis to address the issue as to whether type of surgery might have an impact on overall survival (OS) of young patients with early breast cancer. ⋯ Considering all the limitations, from the present meta-analysis carried out on 22598 patients it appears unlikely that mastectomy provides better OS compared to BCS + WBRT in early breast cancer patients aged 40 years or younger.
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Review Meta Analysis
Postoperative Tamoxifen for ductal carcinoma in situ: Cochrane systematic review and meta-analysis.
This review aimed to assess the effects of postoperative Tamoxifen following surgical resection of ductal carcinoma in situ (DCIS). Data on local DCIS recurrence, new invasive carcinoma, distant disease, mortality and adverse effects were extracted from randomised controlled trials (RCTs) comparing Tamoxifen after surgery for DCIS (regardless of oestrogen receptor (ER) status), with or without adjuvant radiotherapy. Meta-analysis was performed using the fixed-effect model and the results expressed as relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs). ⋯ There was no evidence of a difference in all-cause mortality (RR 1.11; 95% CI 0.89-1.39). Only one trial involving 1799 participants followed-up for 163 months (median) reported on adverse events with no significant difference in event rate between Tamoxifen and placebo groups, but there was a non-significant trend towards more endometrial cancer in the Tamoxifen group. This review concludes that while Tamoxifen after local excision for DCIS, with or without adjuvant radiotherapy, reduced the risk of recurrent DCIS, it did not reduce the risk of all-cause mortality.
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Review Meta Analysis
Postoperative Tamoxifen for ductal carcinoma in situ: Cochrane systematic review and meta-analysis.
This review aimed to assess the effects of postoperative Tamoxifen following surgical resection of ductal carcinoma in situ (DCIS). Data on local DCIS recurrence, new invasive carcinoma, distant disease, mortality and adverse effects were extracted from randomised controlled trials (RCTs) comparing Tamoxifen after surgery for DCIS (regardless of oestrogen receptor (ER) status), with or without adjuvant radiotherapy. Meta-analysis was performed using the fixed-effect model and the results expressed as relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs). ⋯ There was no evidence of a difference in all-cause mortality (RR 1.11; 95% CI 0.89-1.39). Only one trial involving 1799 participants followed-up for 163 months (median) reported on adverse events with no significant difference in event rate between Tamoxifen and placebo groups, but there was a non-significant trend towards more endometrial cancer in the Tamoxifen group. This review concludes that while Tamoxifen after local excision for DCIS, with or without adjuvant radiotherapy, reduced the risk of recurrent DCIS, it did not reduce the risk of all-cause mortality.
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Diagnosis of breast cancer in young women poses a threat to fertility. Due to a recent trend of delaying pregnancy, an increasing number of breast cancer patients in reproductive age wish to bear children. Health care providers have the responsibility to know how to manage fertility issues in cancer survivors. ⋯ The choice of the suitable strategy depends also on age, type of chemotherapy, partner status and patients' motivation. Various options are available, some established such as embryo and oocyte cryopreservation, some still experimental such as ovarian tissue cryopreservation and ovarian suppression with GnRHa during chemotherapy. An early referral to a reproductive specialist should be offered to patients at risk of infertility who are interested in fertility preservation.