ConclusionsIn the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort. KEY WORDSher2-positive breast cancer, survival, trastuzumab, adjuvant

age at onset, large mean tumor size, high grade and higher incidence of node positivity at presentation compared to what is expected based on tumor size. TN status remains an independent risk factor for distant relapse and survival, with a rapid rise in distant relapse in the first three years after diagnosis 2,7 . additionally, patients with TN breast tumors have an increased propensity for lung and brain metastases, making these tumors especially challenging to treat.Molecular classification of breast cancer has further improved our understanding of the biology of this disease. Five intrinsic molecular subgroups of breast cancer have been described, including luminal a, luminal B, Her2-enriched, normal-like, and basal-like breast cancer (BLBC) 8 . Compared to the highly estrogen-sensitive luminal a subgroup, BLBC has significantly worse clinical outcomes with decreased recurrence free and overall survival 8 . BLBC and TNBC share many pathological, molecular, and clinical features, but they are not equivalent. Studies have demonstrated that not all TNBCs are basal-like 9,10 and not all BLBCs have a TN profile 10 . a study analyzing molecular markers differentiating TN tumor subtypes indicated that only 71% of TN tumors (n = 172) had a basal phenotype 9 . research has also suggested that non-basal TNBC may have a more favorable prognosis 8,10,11 .a "five marker" method has been proposed, combining the absence of er, Pr and Her2 with the expression of either epidermal growth factor receptor (eGFr) or cytokeratin (CK) 5/6, to differentiate BLBC from TNBC. While this method has demonstrated specificity for basal-like cancers, the definition has not been uniformly accepted. In the absence of a consensus regarding the optimal method of defining the basal-like subgroup of patients, TN status remains a clinical surrogate.Unlike patients with er/Pr-positive or Her2-overexpressing subtypes, systemic treatment options for patients with TNBC are limited to cytotoxic chemotherapy due to a lack of clinically-validated molecular treatment targets 12 . Standards have not ABSTRACTTriple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including Her2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.

This article provides an overview of recent advances in chemotherapy that may be used for the treatment of patients with locally advanced or metastatic breast cancer (mbc). Key phase ii and iii trial data for eribulin mesylate, ixabepilone, and nab-paclitaxel, published since 2006, are discussed on the basis of recency, depth, and quality. Eribulin mesylate is the first monotherapy to significantly increase overall survival in patients with pretreated mbc, but nab-paclitaxel offers a novel and safer mode of delivery in comparison with standard taxanes. By contrast, the use of ixabepilone will be limited for now, until the associated neurotoxicity can be better managed. Alongside a brief overview of the other major chemotherapies currently in use, we have aimed to provide a Canadian context for how these novel agents may be integrated into clinical practice.

The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (her2), was the first her2-targeted therapy that clearly demonstrated a significant clinical benefit for women with her2-overexpressing metastatic breast cancer (mbc). However, in recent years it has become increasingly apparent that, when trastuzumab is used in the first-line setting in combination with chemotherapy, most women eventually develop progressive disease. Determining the treatment options available to women who have progressed while on trastuzumab therapy has been hampered by a paucity of high-quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible her2-positive patients), the role of anti-her2 agents for patients who experience a breast cancer relapse has become a clinically relevant question. This manuscript reviews current available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in two key mbc indications: Treatment for women with her2-positive mbc progressing on trastuzumab (that is, treatment beyond progression)Treatment for women with her2-positive mbc recurring following adjuvant trastuzumab (that is, re-treatment)The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other her2-targeted agents emerge.

Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in the neoadjuvant setting.The panel focussed on the use of trastuzumab and other her2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; andpossible choices of chemotherapeutic regimens with trastuzumab.The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other her2-targeted agents emerge.

1022 Background: Pertuzumab binds to the dimerization epitope of the HER2 receptor, inhibits HER dimerization and signal transduction, and induces ADCC. In 2 cohorts of pts (n = 66) with HER2-positive metastatic breast cancer which had progressed during trastuzumab therapy after ≤3 lines of chemotherapy with or without trastuzumab, pertuzumab plus trastuzumab has been shown to be active (CR 7.6%, PR 16.7%, SD ≥6/12 25.8%) (Gelmon et al. ASCO 2008, Abs 1026). To assess the activity of pertuzumab monotherapy in this clinical setting, the protocol was amended to include a 3rd cohort of pts. Methods: Pt selection was not changed except that ≥1 month between the last dose of trastuzumab and study start was required. Pts received pertuzumab monotherapy. If the tumor failed to respond or responded and then progressed, trastuzumab could be added to pertuzumab. 27 pts were to be recruited to ensure that ≥24 were fully evaluable for objective response and stabilization of disease ≥6 months. Standard 21-day schedules of the antibodies were given. Results: 29 pts were recruited. Tolerability was good: the major adverse events were mild diarrhea and rash with no clinical cardiac events. To date, 2 responses have been reported, and several pts have ongoing stabilization of disease. 14 pts have received trastuzumab plus pertuzumab following inadequate response (or response then relapse) on pertuzumab monotherapy. Of these 14, 2, having progressed during trastuzumab, failed to respond to pertuzumab monotherapy but underwent confirmed response when trastuzumab was added to the pertuzumab –possibly the first report of such a phenomenon and providing good evidence of an enhanced effect when the antibodies are combined. Updated results will be presented. Conclusions: Pertuzumab monotherapy is active against HER2-positive breast cancer which has progressed during trastuzumab-based therapy. The combination of the two antibodies appears to be more active than either antibody alone. The combination is also active in patients that had failed both antibodies given separately. In clinical studies, the use of the two antibodies combined is justified. [Table: see text]

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18561 Background: Understanding the nature of Internet use among cancer patients is important to facilitate patient-education interventions and for providing optimal patient care. This questionnaire study is designed to evaluate Internet use by cancer patients at a cancer centre. Methods: Cancer patients attending ambulatory clinics at a single Canadian cancer centre were approached by their health care staff. Participants filled out self-administered questionnaire collecting information on demographics, frequency of Internet usage, timing of Internet use during treatment course, type of information sought, and information on patient’s comfort level and satisfaction with Internet use. Results: Of the total 250 participants, 174 (70%) had used the Internet before and 76 (30%) had never used the Internet. Users were more likely to be younger, female, have English as their first language, and be of Caucasian descent. Individuals with breast cancer were also more likely to have used the Internet than pts with other malignancies. Of the Internet users (n = 174), the majority (87%, n = 152) accessed the Internet once per week or more, and felt strongly confident (44%, n=76) in navigating the Internet. 29 users (17%) felt that the information on the Internet was not trustworthy. Of the users, 136 (78%) used the Internet to access information on cancer, and reportedly more often before visiting the cancer centre (50%, n = 70) and before starting initiating cancer treatment (78%, n = 106). The users seeking information on cancer were most likely to look for information on cancer treatment (87%, n = 118) and side effects (74%, n = 100). The top three visited sites were those for Canadian cancer society, Google, and American cancer society. Conclusions: Despite wide availability and accessibility of Internet, it is still not being used as a cancer information tool by many of our patients. By ensuring that accurate and comprehensive information is available on the Internet, perhaps even more patients will use this medium as their information resource, to better understand their diagnosis and make optimal treatment decisions. No significant financial relationships to disclose.