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After more than two decades of intensive research, tremendous progress has been achieved in the management of Human Epidermal Receptor-2 overexpressing (Her2+) Early Breast Cancer (EBC). In the latest years, major clinical trials have explored the neoadjuvant scenario, in addition to the prognostic role of pathologic complete response (pCR) and the possibility of a 'tumor biology-driven' patient selection provided by the assessment pathologic response. However, the introduction of new agents has been a major burden for financially-constrained healthcare systems–which includes those from most emerging markets (currently representing 85% of the world population) but also, to some extent, public systems from welfare states. This manuscript addresses evidence-based opportunities to promote a more rational utilization of the available resources in Her2+ EBC, in addition to areas of interest for future research in cost-efficiency. • Major progress has been achieved in the management of Her2+ Early Breast Cancer. • The neoadjuvant setting and pathologic response have been widely explored in trials. • Financially-constrained healthcare systems have struggled to introduce new agents. • There are opportunities to promote a more rational utilization of the resources. • Financially-constrained healthcare systems should focus on cost-efficiency research. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is frequently used for post-operative treatment in breast cancer (BC) patients who received preoperative systemic therapy (PST) and surgery. Nevertheless, the optimal timing to start RT is unclear. Data from BC patients who underwent chemotherapy as PST, breast surgery and RT at 3 Institutions in Brazil and Canada from 2008 to 2014 were evaluated. Patients were classified into three groups regarding to the time to initiation of RT after surgery: <8 weeks, 8–16 weeks and >16 weeks. A total of 1029 women were included, most of them (59.1%; N = 608) had clinical stage III. One hundred and forty-one patients initiated RT within 8 weeks, 663 between 8 and 16 weeks and 225 beyond 16 weeks from surgery. With a median follow-up of 32 months, no differences in disease-free survival (DFS), overall survival and locoregional recurrence-free survival (LRRFS) were observed of time to indicated RT (<8 weeks versus 8–16 weeks versus >16 weeks). However, in luminal subtype patients (46.5%; N = 478), initiation of RT up to 8 weeks after surgery was associated with better LRRFS (<8 weeks versus >16 weeks: HR 0.22; 95%CI 0.05–0.86; p = 0.03), with a tendency to a better DFS (<8 weeks versus >16 weeks: HR 0.50; 95%CI 0.25–1.00). RT initiated up to 8 weeks after surgery was related to better LRRFS in luminal BC patients who underwent PST. Our results suggest that early start of RT is important for these patients. • RT is used for treatment in breast cancer patients who received chemotherapy as preoperative systemic therapy (PST). • The optimal timing to start RT is unclear. • RT initiated up to 8 weeks after surgery was related to better local control in luminal BC patients who underwent PST. [ABSTRACT FROM AUTHOR]

Abstract Background/Aim Post-operative radiation therapy (PORT) is associated with improvement in loco-regional control and survival rates in early breast cancer. However, the evidence of benefit in patients after treatment with neoadjuvant chemotherapy (NAC) is poor. We aimed to assess the impact of the type of surgery in the PORT plan and the role of the PORT fields in clinical outcomes in breast cancer patients who had undergone NAC followed by surgery. Materials and methods We performed a retrospective analysis of all non-metastatic breast cancer patients treated between 2008 and 2014 at our institution who had received NAC and PORT. Results A total of 528 women were included of whom 396 were submitted to mastectomy or nipple-sparing/skin-sparing mastectomy. Most (92.8%) of the patients had locally advanced disease (clinical stage IIB to IIIC). All patients underwent irradiation for breast or chest wall. Most patients received PORT to the supraclavicular and axillary (levels II and III) nodes (87.1% and 86.4% for breast-conserving surgery and 95.1% and 93.8% for mastectomy and nipple-sparing/skin-sparing mastectomy, respectively). Irradiation of level I axillary and internal mammary nodes was uncommon. The disease-free survival and overall survival rates at 3 years were 72% and 85%, respectively. There were no statistically significant differences in clinical outcomes according to the use of nodal irradiation. Conclusions After NAC, most patients received irradiation of the breast/chest wall and axillary and supraclavicular nodes. In this setting, PORT to breast/chest wall with or without regional nodal irradiation was safe and effective, with acceptable disease-free and overall survival rates reported in this high-risk population. [ABSTRACT FROM AUTHOR]

Background and Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown. Material and methods We retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8–16 weeks and >16 weeks. Results A total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8–16 weeks: HR 0.33; 95% CI 0.13–0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15–0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8–16 weeks: HR 0.22; 95% CI 0.05–0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07–1.15; p = 0.08). Conclusion PORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions. [ABSTRACT FROM AUTHOR]

Objectives This study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site. Material and methods Between 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation. Results 2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001). Conclusion RT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1–3 metastatic sites), and the use of hormone therapy. [ABSTRACT FROM AUTHOR]

Abstract: In recent years, a number of new molecules – commonly known as biological therapies – have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management. [Copyright &y& Elsevier]

Abstract: Targeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer. In this paper we systematically review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions. All trials of HER2-targeted neoadjuvant therapy were identified through non-date-limited searches of PubMED® and Biosis® and congress abstract book searches from 2000–2011. Eligible trials were prospective, had at least 10 patients and a clear definition of pathological complete response (pCR) rate. A total of 50 trials fulfilled the eligibility criteria; 41 single-arm phase II studies were identified, 37 with trastuzumab and 4 with lapatinib, with significant variability in baseline tumour characteristics and pCR rates (range 12–66.7%). Of 9 randomised phase II/III trials, 4 assessed the addition of trastuzumab to chemotherapy and a further 5 randomised trials assessed different HER2-targeting approaches. Four of these studies assessed dual HER2-targeting approaches, which universally increased pCR at the expense of increased non-cardiac toxicity when lapatinib, but not pertuzumab, was added to trastuzumab. Significant advances have been made in HER2 targeting, resulting in a marked increase in the number of breast cancer patients experiencing tumour pCR. Mature data from randomised neoadjuvant and adjuvant studies are awaited for survival outcomes with combination targeted approaches. Unanswered questions centre on the individualisation of therapy and include; which, if any, chemotherapy backbone should be used, and which patients need dual HER2 blockade? [Copyright &y& Elsevier]

The article presents a discussion about the use of panitumumab against colorectal cancer (CRC). In Western countries, the second leading cause of death by cancer is CRC. In phase I to II trials, it was found that patients with CRC tolerated the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody. The most common adverse effect seen in patients was skin toxic effect.

Summary: The discovery of cytotoxic agents was revolutionary for anticancer therapy in the last century, improving survival rates and the quality of life of patients with different types of tumours. However, the development of agents that combine efficacy, safety and convenience remains a great challenge, due to the narrow therapeutic index of some drugs, the fact that they may damage not only cancer cells, but also normal and healthy tissue and the occurrence of resistance, limiting anticancer efficacy. Novel cytotoxic agents have brought certain advantages over the conventional ones, such as shorter administration time, mechanisms to overcome drug resistance and lower incidence of adverse events. In this review we highlight the development of promising novel cytotoxic drugs that will hopefully offer not only gains in efficacy, but also in safety, tolerability and convenience in the treatment of patients with cancer. [Copyright &y& Elsevier]

Summary: Her2 and topoisomerase-IIα (T2A) gene amplification are separate events, although the latter is more frequently seen in Her2 amplified (34–90%) than in Her2 non-amplified (5–10%) tumours. There is a better correlation between Her2 amplification and protein overexpression in breast cancer (BC) than in other tumour types. This marker is also considered a powerful prognostic factor in BC, with similar data emerging in other solid tumours such as bladder, ovarian, endometrial, gastro-oesophageal and non-small cell lung cancer. Her2 amplification and/or overexpression are highly predictive of response to HER2-targeted compounds such as trastuzumab and lapatinib but have been inconsistent predictors of response to cytotoxic chemotherapy. There is also evidence that these tumours are relatively resistant to anti-oestrogen therapy (tamoxifen) but not to oestrogen deprivation (e.g. with aromatase inhibitors). T2A aberrations are uncommon events in solid tumours, with an overall prevalence of approximately 10%. T2A amplification has shown inconsistent correlation with T2A protein expression in preclinical and clinical studies, mainly because non-genetic events such as proliferation rate can also affect protein expression. Expression of T2A protein has not been shown to reliably predict response to T2A inhibitors, despite the fact that this enzyme is the direct target for these compounds. In BC, T2A amplification appears to be a good predictor of response to anthracyclines, but these data are still in the process of validation. The significance of T2A deletions is currently under investigation, but contrary to what was previously thought, it may also predict benefit from treatment with T2A inhibitors. The prognostic significance of T2A aberrations is currently unknown. [Copyright &y& Elsevier]

Summary: Vinorelbine is a semi-synthetic vinca alkaloid that has been shown active in many tumour types and is currently registered for the treatment of advanced breast cancer (ABC) and non-small cell lung cancer (NSCLC). This agent has a generally favourable safety profile, and may be suitable for use in special populations such as the elderly and/or frail patient. However, with the taxanes firmly established as standard second line treatment for ABC after failure of an anthracycline, vinorelbine has been generally relegated for use as third line therapy, in competition with the oral compound capecitabine. More recently, the exciting results observed with the combination of vinorelbine and trastuzumab in patients with Her-2 overexpressing/amplified tumours, as well as the development of a reliable formulation and revised schedule of oral vinorelbine with proven activity in ABC appear to have revived the interest in this compound in the management of this disease. There are still a number of unanswered questions that will have to be addressed by properly designed, adequately powered randomised clinical trials. [Copyright &y& Elsevier]

Summary: The rationale to justify the use of anthracyclines as adjuvant therapy for breast cancer is their proven superiority over CMF. Indeed, this has been demonstrated by a number of randomised clinical trials and recently confirmed by the Oxford meta-analysis. Nevertheless, the absolute benefit is modest (on average 4%), and with the cost of increased toxicity. Interestingly, many individual trials were unable to confirm the role of anthracyclines in early breast cancer, though most of these were either underpowered to show such small differences, or had inappropriate experimental arms. On the other hand, several trials included in the meta-analysis also had inadequate control arms. So far, probably only three trials were able to individually confirm this benefit: the American INT 0102, the Canadian MA5 and more recently, the British NEAT/NCTBG. Numerous different anthracycline schedules have been used as adjuvant therapy, many of these having never been compared to CMF. Unfortunately, as research is moving towards other more important questions, many of these uncertainties may never be clarified. In this paper, we review the current evidence behind some of the most commonly used anthracycline schedules. [Copyright &y& Elsevier]

Summary: The liver is a common site of metastases in breast cancer. Although the development of liver metastases has long been associated with a poor prognosis in this disease, this dogma has been challenged by more recent data, perhaps reflecting some treatment and other technological advances achieved in the last decade. Nevertheless, the specific population of breast cancer patients presenting with liver disease and associated liver dysfunction remain poorly studied. These women still seem to have a poor prognosis as compared to other patients with liver metastases. This is further complicated by the fact that the most active cytotoxic agents in breast cancer have significant hepatic metabolism and/or biliary excretion. Unfortunately, since these patients have been most of the time excluded from clinical trials, there are currently no clear recommendations for the management of such dramatic presentations. With some exceptions, recommendations for dose adjustments have also been largely empirical. In this paper, we review the optimal doses of cytotoxics used in this clinical situation and provide some tips on the management of these patients, based on the limited data currently available in the literature. [Copyright &y& Elsevier]

Summary: The use of diethylstilbestrol (DES) for high risk pregnancy has exposed millions of mothers to an increased risk of breast cancer, and also resulted in a generation of women with genital tract abnormalities, such as vaginal adenosis. It is still too early to say that exposure to DES will also result in an increased risk of breast cancer in the offspring, though there is some preliminary evidence to support this. The employment of optimal hormonal therapy (for breast cancer) in this special population may be hampered by the fact that agents with oestrogen agonistic activity (such as tamoxifen) may be contraindicated. Though some of the newer hormonal agents, such as the pure anti-oestrogen Fulvestrant and the aromatase inhibitors, could be considered interesting alternatives for postmenopausal patients, their safety in this population has never been evaluated. Finally, the prevalence prenatal exposure to DES may have been underestimated patients diagnosed with breast cancer, though this information might have major implications in their management. We report on the interesting example of a young woman with a history of vaginal adenosis, who was also diagnosed with early breast cancer. [Copyright &y& Elsevier]

Summary: We report on the case of a patient with a diagnosis of an uncommon breast tumour, namely a radiation-induced angiosarcoma, which was primarily refractory to anthracycline-based chemotherapy, but highly sensitive to docetaxel. Although the sarcomas in general tend to be relatively refractory to taxanes, there is some evidence that the angiosarcomas may be sensitive to these agents. This is particularly well documented with paclitaxel, but may also be the case with docetaxel. [Copyright &y& Elsevier]