https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61121-X.pdf

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial

Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

/pdf/microenvironmental-regulation-of-tumor-progression-and-4528oymlw6.pdf

Microenvironmental regulation of tumor progression and metastasis.

Purpose To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. Methods The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Results Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. Recommendations The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly...

/pdf/american-society-of-clinical-oncology-college-of-american-5b47o39c65.pdf

American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer

Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011

A b s t r ac t The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. Conclusions Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2- positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa064320

Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer

1055 Background: In pts with Her2 positive ABC, taxane or vinorelbine plus T are among the most widely applied options in the first line setting. We evaluated the efficacy and tolerability of TC in...

Trastuzumab (T) plus capecitabine (C) in heavily pretreated patients (pts) with advanced breast cancer (ABC)

Breast cancer is the most common malignancy in women in Western Europe and the U.S. Adjuvant chemotherapy reduces the rate of cancer recurrence, thereby contributing to the recent decline of breast cancer mortality. Notably, a number of important developments occurred over the past decades. Starting with first generation regimens like CMF, the next step was the introduction of anthracyclines into the adjuvant setting, although the role of these drugs is again dubious today. Modern regimens followed with the introduction of taxanes into the adjuvant setting, and a number of further developments are under way: Dose dense regimens as well as targeted therapies have led to a new era of treatment of women with early breast cancer. Neoadjuvant chemotherapy, while sometimes still debated, has increased the rate of breast conserving surgeries. Obviously, both neoadjuvant, therefore preoperative, and adjuvant chemotherapy have their specific advantages and drawbacks. This will be dealt with in detail. Also a short overview of available data on adjuvant chemotherapy in the elderly is provided. The history, recent developments, as well as open questions will be discussed in this review.

Adjuvant chemotherapy in breast cancer

P347 Benefit of denosumab therapy in patients with bone metastases from breast cancer: A number-needed-to-treat (NNT) analysis

Safety and effectiveness of nab-paclitaxel in young and elderly patients with metastatic breast cancer: a prospective, multicenter non-interventional study

708 Background: FUL is an estrogen receptor (ER) antagonist for the treatment of postmenopausal women with hormone-dependent advanced breast cancer (ABC). Our pilot study evaluated the efficacy and safety of FUL in premenopausal women with hormone-sensitive ABC rendered postmenopausal with continuous GOS treatment. Methods: This prospective trial included 14 patients (pts) with ER and/or progesterone receptor-positive ABC. 2 pts were human epidermal growth factor receptor 2-positive (HER2+). Pts received at least 3 doses of FUL 250 mg i.m. q 4 weeks and continued to receive GOS 3.6 mg sc q 4 weeks until disease progression or intolerability. Tumor assessment and evaluation of time to disease progression (TTP) occurred every 3 cycles. Results: 14 pts (median age 41 years, range 28–49) were included in this evaluation. 1 pt received GOS + FUL as 1st-line therapy, 7 as 2nd-, 5 as 3rd-, and 1 as 4th-line treatment, respectively. 11 pts (78.6%) had received adjuvant chemotherapy and 8 pts (57.1%) adjuvant endo...

Günther G. Steger

Papers

Trastuzumab (T) plus capecitabine (C) in heavily pretreated patients (pts) with advanced breast cancer (ABC)

Adjuvant chemotherapy in breast cancer

P347 Benefit of denosumab therapy in patients with bone metastases from breast cancer: A number-needed-to-treat (NNT) analysis

Safety and effectiveness of nab-paclitaxel in young and elderly patients with metastatic breast cancer: a prospective, multicenter non-interventional study

Fulvestrant (FUL) and goserelin (GOS) in premenopausal women with advanced, hormone-sensitive breast cancer: A pilot study