Locoregional therapy of locally advanced breast cancer: a clinical practice guideline.

QUESTIONS: In female patients with locally advanced breast cancer (labc) and good response to neoadjuvant chemotherapy (nact), including endocrine therapy, what is the role of breast-conserving surgery (bcs) compared with mastectomy?In female patients with labc, is radiotherapy (rt) indicated for those who have undergone mastectomy?does locoregional rt, compared with breast or chest wall rt alone, result in a higher survival rate and lower recurrence rates?is rt indicated for those achieving a pathologic complete response (pcr) to nact?In female patients with labc who receive nact, is the most appropriate axillary staging procedure sentinel lymph node biopsy (slnb) or axillary dissection? Is slnb indicated before nact rather than at the time of surgery?How should female patients with labc that does not respond to initial nact be treated? METHODS: This guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care (pebc) and the Breast Cancer Disease Site Group (dsg). A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period 1996 to December 11, 2013. Guidelines were located from that search and from the Web sites of major guideline organizations. The working group drafted recommendations based on the systemic review. The systematic review and recommendations were then circulated to the Breast Cancer dsg and the pebc Report Approval Panel for internal review; the revised document underwent external review. The full three-part evidence series can be found on the Cancer Care Ontario Web site. RECOMMENDATIONS: For most patients with labc, modified radical mastectomy should be considered the standard of care. For some patients with noninflammatory labc, bcs can be considered on a case-by-case basis when the surgeon deems that the disease can be fully resected and the patient expresses a strong preference for breast preservation.For patients with labc, rt after mastectomy is recommended.It is recommended that, after bcs or mastectomy, patients with labc receive locoregional rt encompassing the breast or chest wall and local node-bearing areas.It is recommended that postoperative rt remain the standard of care for patients with labc who achieve pcr to nact.It is recommended that axillary dissection remain the standard of care for axillary staging in labc, with the judicious use of slnb in patients who are advised of the limitations of the current data.Although slnb either before or after nact is technically feasible, the data are insufficient to make any recommendation about the optimal timing of slnb with respect to nact. Limited data suggest higher sentinel lymph node identification rates and lower false negative identification rates when slnb is conducted before nact; however, those data must be balanced against the requirement for two operations if slnb is not performed at the time of resection of the main tumour.It is recommended that patients receiving neoadjuvant anthracycline-taxane-based therapy (or other sequential regimens) whose tumours do not respond to the initial agent or agents, or who experience disease progression, be expedited to the next agent or agents of the regimen.For patients who, in the opinion of the treating physician, fail to respond or progress on first-line nact, several therapeutic options can be considered, including second-line chemotherapy, hormonal therapy (if appropriate), rt, or immediate surgery (if technically feasible). Treatment should be individualized through discussion at a multidisciplinary case conference, considering tumour characteristics, patient factors and preferences, and risk of adverse effects.It is recommended that prospective randomized clinical trials be designed for patients with labc who fail to respond to nact so that more definitive treatment recommendations can be developed.

Patient adherence to aromatase inhibitor treatment in the adjuvant setting.

Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider-related. To date, there is a gap in the literature concerning a comprehensive understanding of factors related to medication adherence with anti-estrogen therapy in the adjuvant setting. The literature suggests that strategies for improving adherence should focus on education of patients, assessment of the ability of patients to understand their disease and related recurrence factors, and facilitation of adherence by patients by providing adequate support and strategies for good self-management. However, more research is needed to better understand how health care providers can support women with breast cancer on oral therapy in the adjuvant setting.

Models of care for early-stage breast cancer in Canada.

There is growing evidence that follow-up for patients with early breast cancer (ebc) can be effectively carried out by the primary health care provider if a plan is in place. Here, we present data from a recent survey conducted in Ontario indicating that a shared-care model could work if communication between all health professionals involved in the care of ebc patients were to be improved. Patients and primary care providers benefit when the specialist provides written information about what their roles are and what to expect. Primary care providers need to have easy access to the specialist to discuss areas of concern. Patients also need to share responsibility for their care, ensuring that they attend follow-up visits on a regular basis and that they discuss areas of concern with their primary health care provider. A shared-care model has the potential to provide the best care for the least cost to the health system.

Real-world experience with adjuvant fec-d chemotherapy in four Ontario regional cancer centres.

BACKGROUND: The efficacy of adjuvant chemotherapy with fec-d (5-fluorouracil-epirubicin-cyclophosphamide followed by docetaxel) is superior to that with fec-100 alone in women with early-stage breast cancer. As the use of fec-d increased in clinical practice, health care providers anecdotally noted higher-than-expected toxicity rates and frequent early treatment discontinuations because of toxicity. In the present study, we compared the rates of serious adverse events in patients who received adjuvant fec-d chemotherapy in routine clinical practice with the rates reported in the pacs-01 trial. METHODS: We retrospectively reviewed all patients prescribed adjuvant fec-d for early-stage breast cancer at 4 regional cancer centres in Ontario. Information was collected from electronic and paper charts by a physician investigator from each centre. Data were analyzed using chi-square tests, independent samples t-tests, one-way analysis of variance, and univariate regression. RESULTS: The 671 electronic and paper patient records reviewed showed a median patient age of 52.2 years, 229 patients (34.1%) with N0 disease, 508 patients (75.7%) with estrogen or progesterone receptor-positive disease (or both), and 113 patients (26%) with her2/neu-overexpressing breast cancer. Febrile neutropenia occurred in 152 patients (22.7%), most frequently at cycle 4, coincident with the initiation of docetaxel [78/152 (51.3%)]. Primary prophylaxis with hematopoietic growth factor support was used in 235 patients (35%), and the rate of febrile neutropenia was significantly lower in those who received prophylaxis than in those who did not [15/235 (6.4%) vs. 137/436 (31.4%); p < 0.001; risk ratio: 0.20]. CONCLUSIONS: In routine clinical practice, treatment with fec-d is associated with a higher-than-expected rate of febrile neutropenia, in light of which, primary prophylaxis with growth factor should be considered, per international guidelines. Adoption based on clinical trial reports of new therapies into mainstream practice must be done carefully and with scrutiny.

Failure of ovarian ablation with goserelin in a pre-menopausal breast cancer patient resulting in pregnancy: a case report and review of the literature.

To report an unanticipated pregnancy during ovarian ablation treatment with goserelin (10.8 mg SC every 12 weeks) in a 26-year old female with breast cancer. Review of the current literature and reports in MEDLINE, PubMED, and EMBASE using searches with keywords "goserelin, pregnancy, breast cancer, breast neoplasms, fertility, ovarian ablation, gonadotropin releasing hormone agonists/analogs, leuprolide, pregnancy complications, teratogens" (July-September 2010). Only 3 other reports of failures with goserelin administration at ablative doses in breast cancer patients were discovered. For physicians and breast cancer patients using a GnRH analog, it is important to be aware of the possibility of inadequate ovarian function suppression and the potential for pregnancy.

An updated review on the efficacy of adjuvant endocrine therapies in hormone receptor-positive early breast cancer.

The third-generation aromatase inhibitors (AIS) are largely replacing tamoxifen in the adjuvant treatment of early-stage breast cancer in postmenopausal women with hormone receptor-positive tumours. To date, multiple trials have been conducted comparing tamoxifen treatment with an AI, and all have demonstrated improved disease-free survival with AI treatment. Trials have included direct 5-year comparisons between tamoxifen and an AI, switching to an AI within 5 years after initial tamoxifen treatment, or extending treatment with an AI after 5 years of completed tamoxifen treatment. Some of these trials have been completed; others are ongoing; and head-to-head trial comparisons of individual AIS are also in progress. The present article summarizes the data obtained from various clinical trials of hormonal therapy for early breast cancer. It also reviews recent data so as to shed light on the current status of these therapies. The focus is on the efficacy of treatment with an AI. Toxicity is discussed in the second article in this supplement.

Are medical oncologists biased in their treatment of the large woman with breast cancer?

PURPOSE: Obesity and breast cancer are common conditions that often coexist. Concerns of relative overdosing of chemotherapy in the large cancer patient have led clinicians to apply empiric dose reductions, 'cap' the body surface area (BSA) at 2 m2, or use ideal rather than actual body weight to calculate BSA. There are no data supporting or refuting these practices and their prevalence is unknown. We sought to determine the distribution of body size and prevalence of obesity in the breast cancer population of our cancer centre, and to determine clinician chemotherapy dosing practices in the era of modern adjuvant chemotherapy. PATIENTS AND METHODS: Women with invasive breast cancer receiving systemic therapy at our institution between 1980 and 1998 were identified and their recorded height and weight were used to calculate BSA and body mass index (BMI). We reviewed the first cycle adjuvant chemotherapy dosing practices from 1990-1998. The ideal dose of chemotherapy was calculated based on calculated BSA, and then contrasted with the actual dose received at cycle one. Discrepancies were recorded and categorized, using the largest single drug reduction if more than one drug was reduced. RESULTS: Mean BMI in the systemic therapy population was 26.4 +/- 5.3 kg/m2, 54% were overweight, 2% severely obese and 18% moderately so. Their mean BSA was 1.7 +/- 0.2 m2 and only 5% had a BSA > or = 2 m2. In the adjuvant chemotherapy subgroup, most patients received > or = 85% of their ideal dose. The mean dose reduction was 5.3 +/- 11.3% versus 9.9 +/- 11.3% in the BSA < 2 and > or = 2 m2 groups, respectively (p = 0.02), and 4.3 +/- 8.2% versus 6.7 +/- 13.1% in the BMI < 25 and > or = 25 kg/m2 groups, respectively (p = 0.008). While only 24% of chemotherapy dose reductions of > or = 15% were in the BSA > or = 2 m2 group, 76% were in the BMI > or = 25 kg/m2 group. CONCLUSIONS: Obesity is prevalent in this breast cancer population. BSA is not a sensitive index of large body size. We consistently detected more frequent empiric dose reductions at cycle one of adjuvant chemotherapy, with reductions of greater magnitude in the largest women (BSA > or = 2 m2) and those who were overweight (BMI > or = 25 kg/m2).

Irinotecan-associated pulmonary toxicity.

We present the circumstances surrounding a 57-year-old Caucasian man with advanced colorectal cancer who developed relapsing interstitial lung disease following a single exposure to irinotecan (CPT-11). Progressive pulmonary insufficiency and death were reported in the initial Japanese studies, despite institution of empiric steroid therapy for a syndrome similar to that which our patient experienced. As a result, patients with compromised pulmonary function were generally excluded from US clinical trials. Notwithstanding this, cough and dyspnea were reported in approximately 20% of patients in the US studies. As the clinical indications for the use of this agent expand, we describe irinotecan-associated interstitial pneumonitis as a serious potential adverse effect. Patients with pre-existing pulmonary disease may be at higher risk for this complication and clinicians should be alert to this possibility.