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Background Studies in the adjuvant setting suggest that the timing of breast cancer diagnosis, surgery, and chemotherapy might affect outcomes. In the neoadjuvant setting, data exploring whether expeditious neoadjuvant chemotherapy (nac) after diagnosis improves the rate of pathologic complete response (pcr) in breast cancer are limited. Methods Patients who received nac and completed treatment between May 2012 and December 2018 were identified from a prospectively collected database at BC Cancer. Time from diagnosis to start of nac was calculated. Patients were grouped into those who did and did not experience a pcr, and those who started nac within 28 days or after 28 days [time to nac (ttn)]. The association between pcr and ttn was tested using logistic regression. Results In the time period studied, 482 patients who received nac were identified. After exclusions, 421 patients met the eligibility criteria. Median time from biopsy to chemotherapy was 33 days (range: 7-140 days). In 149 patients (35.4%), nac was received within 28 days of diagnosis (range: 7-28 days); in 272 patients (64.6%), it was received after more than 28 days (range: 29-140 days). The overall pcr rate was 31.8%. A trend toward a higher pcr rate, although not statistically significant, was observed in the group that initiated chemotherapy within 28 days (34.2% vs. 30.5%, p = 0.43). In the logistic regression model, rates of pcr were associated with receptor status, but not age, stage, or ttn. Conclusions In the neoadjuvant setting, we observed no difference in the rate of pcr in patients who started nac within 28 days or after 28 days. [ABSTRACT FROM AUTHOR]

Background The use of Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) testing has been shown to change treatment decisions in approximately 30% of breast cancer (bca) cases, but research on how Recurrence Score testing has affected the type of chemotherapy offered is limited. We sought to determine if the availability of Oncotype dx testing resulted in a change to the type and duration of chemotherapy regimens used in the treatment of early-stage hormone receptor-positive bca. Methods In a population-based cohort study, patients treated in the 2 years before the availability of Oncotype dx testing were compared with patients treated in the 2 years after testing availability. Charts were audited and divided into 2 groups: pre-Oncotype dx and post-Oncotype dx. The groups were compared for differences in duration of chemotherapy (12 weeks vs. >12 weeks), types of agents used (anthracycline vs. non-anthracycline), and myelosuppressive potential of the chosen regimen. Results Of 834 patients who fulfilled the enrolment criteria, 360 fell into the pre-Oncotype dx era, and 474, into the post-Oncotype dx era. An increase of 11.2 percentage points, to 69.5% from 58.3%, was observed in the proportion of patients receiving short-course compared with long-course chemotherapy (p = 0.068). The proportion of patients prescribed anthracycline-containing regimens declined in the post-Oncotype dx era (47.7% pre vs. 32.2% post, p = 0.016). The selection of more-myelosuppressive chemotherapy protocols increased in the post-Oncotype dx era (67.4% pre vs. 78.8% post, p = 0.044). Conclusions In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca. [ABSTRACT FROM AUTHOR]

Therapy for breast cancer involves a complex interplay of three main treatment modalities: surgery, systemic therapy, and radiation therapy. The Canadian Consortium for Locally Advanced Breast Cancer (LABC) was established with the goal to convene a strong multidisciplinary team of breast oncology clinicians and scientists who are dedicated to the advancement of LABC research and treatment, with a vision to drive progress through increased collaboration across disciplines and throughout Canada. The most recent meeting in May 2017 highlighted the latest evidence and literature about the optimal use of neoadjuvant systemic therapy in breast cancer. There is a need for increased clinical and scientific collaboration and the development of guidelines for the use of emerging treatment strategies. The interactive meeting sessions fostered unique opportunities for academic debate and nurtured collaboration between the attendees. [ABSTRACT FROM AUTHOR]

Background The use of neoadjuvant systemic therapy (NAST) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (RT) in that setting is uncertain. We sought to review and report the use of NAST, its trends over time, and its relationship with the prescribing patterns of locoregional RT in a provincial cancer system. Methods Patients with stages I-III breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of NAST. Kaplan-Meier and Cox regression were used for survival analyses. Results Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received NAST. Use of NAST was more frequent in stage III patients (53%) than in stages I and II patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of NAST and of nodal RT after NAST, but pathologic nodal status after NAST was not associated with use of nodal RT. A statistically significant survival difference was observed between patients in the NAST and no- NAST groups, but that significance disappeared in a multivariable Cox regression analysis. Conclusions This population-based study demonstrated 5% use of NAST for breast cancer. Most patients received nodal RT after NAST, and nodal RT was not associated with pathologic stage after NAST. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature. [ABSTRACT FROM AUTHOR]

Background Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (NAT) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (RCTS) in this area. Methods A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing NAT for breast cancer. All RCTS published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the RCTS were analyzed to determine if the methods used matched the expert consensus for specific areas of NAT management. A scoring system determined the strength of the agreement between the literature and the expert consensus. Results Consensus was achieved for all areas of the pathway of care for patients undergoing NAT for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published RCTS varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. Conclusions A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving NAT for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of NAT management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving NAT. [ABSTRACT FROM AUTHOR]

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The use of systemic therapy before surgery ("neoadjuvant therapy") is the standard of care for the treatment of locally advanced and nonoperable breast cancer. The advantages of neoadjuvant therapy include improved rates of breast-conserving surgery, the possibility of early measurement of response, and potentially improved outcomes for certain subgroups of high-risk patients. The use of neoadjuvant therapy in operable breast cancer is increasing, although there are no clear guidelines in Canada to help guide patient selection and management. Multidisciplinary experts in the diagnosis and treatment of locally advanced breast cancer (LABC) converged at the fourth annual meeting of the Canadian Consortium for LABC (COLAB) to further their goals of improved standards for neoadjuvant care and clinical research through education and collaboration. Canadian clinical researchers were joined by Dr. Michael Untch of the Helios Hospital Berlin-Buch—representing the German neoadjuvant treatment groups German Gynecologic Oncology Working Group (Arbeitsgemeinschaft Gynakologische Onkologie) and German Breast Group—to discuss the advancement of research in the neoadjuvant setting and important issues of clinical care and investigator-led research. The group reached a consensus on the importance of multidisciplinary collaboration, the use of clips to mark tumour location, and core biopsy testing for the estrogen and progesterone receptors and the human epidermal growth factor receptor 2 at the time of diagnosis. Other initiatives—including creation of a prospective database, inception of the COLAB Neoadjuvant Network, and development of a clinical survey to evaluate current practice—continue to further the COLAB mandate of transforming the neoadjuvant treatment landscape in Canada. [ABSTRACT FROM AUTHOR]

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1-68.1). On univariate analysis, cancer type ( p < 0.05) and mGPS ( p < 0.001) were significantly associated with OS. On multivariate analysis, only mGPS ( p < 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS ( p < 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.

Introduction: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC)., Methods: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures., Results: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23-90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control ( n = 9). A few patients ( n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients ( n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29-40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7-64.69) and no LRT (45.27 months; 95% CI: 33.25-58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation., Discussion: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.

Background: The real-world impact of tyrosine kinase inhibitors (tkis) in clinical practice for gastrointestinal stromal tumour (gist) has not been extensively reported. We sought to assess how outcomes have changed over the eras and to evaluate the effect of access to imatinib and sunitinib on survival in patients with unresectable or metastatic gist in British Columbia., Methods: Patients with metastatic or unresectable gist were allocated to one of three eras: pre-2002, 2002-2007, and post-2007 based on treatment availability (pre-imatinib, post-imatinib, and post-sunitinib). Overall survival (os) and progression-free survival (pfs) were compared between eras. Univariate and multivariate analyses were performed to determine the effects of tumour, patient, and treatment characteristics on survival outcomes., Results: Of 657 patients diagnosed with gist throughout British Columbia during 1996-2016, 196 had metastatic disease: 23 in the pre-imatinib era, 67 in the post-imatinib era, and 106 in the post-sunitinib era. A significant increase in os, by 53.6 months ( p = 0.0007), and pfs, by 29.1 months ( p = 0.044), was observed after the introduction of imatinib. The introduction of sunitinib did not significantly affect os or pfs., Conclusions: Implementation of tkis has drastically improved survival outcomes for patients with metastatic gist by up to 4.55 years in the real-world setting. Our study demonstrates that implementation of tkis in clinical practice has outperformed their benefit predicted in clinical trials., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy., Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria., Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival., Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Bone is the most common site for distant spread of breast cancer. Following a diagnosis of metastatic bone disease, patients can suffer from significant morbidity because of pain and skeletal related events (SRES). Bisphosphonates are potent inhibitors of osteoclastic function and the mainstay of bone-directed therapy for bone metastases. The aims of bisphosphonates are to prevent and delay SRES, to reduce bone pain, and to improve quality of life. Bisphosphonate therapy appears to have revolutionized treatment of bone metastases, but bisphosphonate use has several limitations. Those limitations include the high cost of the agents and the need for return trips to the clinic for intravenous treatment. Moreover, many uncertainties surround bisphosphonate use-for example, the timing of bisphosphonate initiation, the choice of bisphosphonate to use, the optimal duration of treatment, and the appropriate means to identify patients who will and will not benefit. In addition, potentially serious adverse effects have been associated with bisphosphonate use-for example, renal toxicity, gastrointestinal side effects, and osteonecrosis of the jaw. The present review is intended as a primer for oncology specialists who treat patients with bone metastases secondary to breast cancer. It focuses on bisphosphonate treatment guidelines, the evidence for those guidelines, and a discussion of new therapeutic agents. It also discusses the use of biochemical markers of bone metabolism, which show promise for predicting the risk of a patient's developing a SRE and of benefiting from bisphosphonate treatment.