Breast Cancer in Elderly Women: is Partial Breast Irradiation a Good Alternative?

Background. Approximately half of all breast cancer occurs after age 65. Several aspects for the treatment of early breast cancer may be influenced by patient age, including postoperative radiation therapy (RT), in order to prevent the risk of local recurrence (LR). Postoperative adjuvant RT, improving the chances of local control, is not always completed because of comorbidity-associated factors. Does an alternative exist between a 5-week radiotherapy regime and no irradiation after breast conservative surgery without burdening the overall therapeutic management? Methods. The authors review the literature regarding age-specific issues in the irradiation of breast cancer and the potential role of a partial breast irradiation (PBI) to prevent LR in the ipsilateral breast. Results. Phase II and III trials have been analyzed for feasibility, efficacy and toxicity. PBI may be delivered with low or high dose rate brachytherapy and intra operative, or external beam radiation therapy. PBI satisfies the control quality criteria. The majority of the teams provide PBI recurrence rates lower than 5% (0–4.4%) with a median follow-up varying between 8 and 72 months, associated with cosmetic results comparable to those achieved with conventional external beam. Conclusions. Breast cancer in elderly women represents a medical and economical problem. The recommended conservative treatment includes RT for 50?Gy over 5 weeks. Some subgroups of patients did not receive radiotherapy because of comorbidity-associated factors or more favorable tumor biology. PBI seems to be an acceptable alternative to adjuvant RT over 5 weeks and no irradiation. The evaluation of toxicity and efficacy, especially in terms of local control, is necessary and large multicentric phase III trials comparing the two irradiation approaches are needed, including quality of life, economic considerations and longer follow-up.     

Zoledronic Acid in the Treatment of Early-Stage Breast Cancer: Is There a Final Verdict?

Breast cancer, which preferentially metastasizes to bone, is the most common malignancy among women worldwide and is a leading cause of death. Clinical data from large, phase 3 trials (ie, ABCSG-12, ZO-FAST, and AZURE) demonstrate significantly improved disease-free survival with zoledronic acid in some patient populations with early breast cancer. Although the interim results from the AZURE trial did not show a disease-free survival benefit with zoledronic acid in the overall patient population, subset analyses showed that zoledronic acid significantly improved disease-free survival in women with established postmenopausal status at baseline. Similarly, subset analyses of the ABCSG-12 trial showed greater benefits from zoledronic acid in patients over 40 years of age who theoretically would have achieved more complete ovarian suppression. Together, these data support a potential role for zoledronic acid beyond bone health in breast cancer and suggest that the endocrine environment may influence the anticancer potential of zoledronic acid.     

Is kV Intraoperative Radiation Therapy an Acceptable Method for Partial Breast Irradiation?

Multiple large prospectively randomized trials of postoperative partial breast irradiation (PBI) have established it as a viable alternative to whole-breast irradiation for risk-adapted breast conserving management of early stage disease. An area of controversy remains regarding the relative efficacy, safety, and utility of intraoperative radiation therapy as a PBI technique. This is particularly true regarding the use of a 50 kV x-ray device, whereby the inherent dosimetry of the applicator results in a low dose of radiation to an exceedingly small volume of tissue. A critical analysis of the current clinical data would strongly support the view that intraoperative radiation therapy with a 50 kV x-ray device is associated with inferior outcomes compared with the variety of currently available modalities used for postoperative PBI.     

Is the Management of Rectal Cancer Using a Watch and Wait Approach Feasible,Safe and Effective in a Publicly Funded General Hospital?

AimsAlthough there is emerging evidence to suggest equivalent oncological outcomes using a watch and wait approach compared with primary total mesorectal excision surgery, there is a paucity of evidence about the safety and efficacy of this approach in routine clinical practice. Here we report the long-term outcomes and quality of life from patients managed with watch and wait following a clinical complete response (cCR) to neoadjuvant therapy.Materials and methodsPatients with adenocarcinoma of the rectum with cCR following neoadjuvant therapy managed using watch and wait were retrospectively identified. Demographic data, performance status, pretreatment staging information, oncological and surgical outcomes were obtained from routinely collected clinical data. Quality of life was measured by trained clinicians during telephone interviews.ResultsOver a 7-year period, 506 patients were treated for rectal cancer, 276 had neoadjuvant therapy and 72 had a cCR (26.1%). Sixty-three were managed with watch and wait. Thirteen patients had mucosal regrowth. There was no significant difference in the incidence of metastatic disease between the surgical and watch and wait cohorts (P = 0.38). The 13 patients with mucosal regrowth underwent salvage surgery. Eleven of the patients who underwent surgical resection had R0 resections. There was also a statistically and clinically significant improvement in the Functional Assessment of Cancer Therapy – Colorectal (FACT-C) trial outcome index (P = 0.022).ConclusionThis study shows that watch and wait is safe and effective outside of tertiary referral centres. It suggests that an opportunistic cCR is durable and when mucosal regrowth occurs it can be salvaged. Finally, we have shown that quality of life is probably improved if a watch and wait approach is adopted.     

Metabolic Syndrome and Breast Cancer Risk: Is There a Role for Metformin?

Obesity is one of the most important known preventable causes of cancer, accounting for up to 20% of cancer deaths in women. Obese women have increased risk of dying from breast cancer as well as an increased risk of distant metastasis. Metabolic Syndrome (MetSyn) is a group of metabolic conditions that include 1) abdominal obesity, 2) atherogenic dyslipidemia, 3) elevated blood pressure, and 4) insulin resistance. MetSyn is known to promote the development of cardiovascular disease and diabetes and may be associated with increased breast cancer risk. Emerging evidence supports an association between mammary adipocytes and their secreted adipocytokines and breast cancer initiation and progression. Metformin (1,1-dimethylbiguanide hydrochloride) is a drug used to treat type 2 diabetes and MetSyn. We review the potential association between MetSyn in promoting breast cancer and emerging evidence for the use of metformin in cancer prevention.     

Utility of GnRH-Agonists for Fertility Preservation in Women with Operable Breast Cancer: Is It Protective?

Breast cancer is the most common type of malignancy in reproductive-age women. Breast cancer chemotherapy is associated with premature ovarian failure, infertility, and negative psychosocial effects related to these reproductive changes. As a result of this, fertility preservation becomes highly critical in this group of women. Besides the fertility preservation methods that utilize assisted reproductive technologies such as embryo, oocyte, and ovarian tissue cryopreservation, another suggested strategy for fertility preservation is suppression of ovarian ovulatory function by gonadotropin-releasing hormone agonist (GnRHa) administration before and during chemotherapy. However, both the efficacy and safety of GnRH agonists for prevention of ovarian damage are unproven and the preponderance of evidence indicates that this is an ineffective strategy. This review details the most recent information and studies on this controversial topic.     

Patients With Metastatic Breast Cancer Using Bevacizumab as a Treatment: Is There Still a Role for it?

OPINION STATEMENT: Over the last few decades, the angiogenesis mechanism has increasingly been studied and implicated in cancer pathophysiology. At present, it is known that angiogenesis plays a relevant role in tumor growth, and more importantly many new molecules exists can potentially interfere with this process. Bevacizumab, a humanized monoclonal antibody targeting the vascular endothelial growth factor A (VEGF-A) now commonly used in the treatment of colorectal, renal cell, and brain cancer, is the first anti-angiogenesis drug delivered in combination with chemotherapy that has consistently shown clinical efficacy in the treatment of breast cancer. Since the ECOG 2100 trial has shown that bevacizumab added to paclitaxel as a first-line treatment for advanced breast cancer nearly doubled the time to progression and tumor response rate, its approval was granted almost worldwide. However, other phase III trials revealed a smaller absolute improvement in progression-free survival (PFS) and response rates, and no trials yet have demonstrated survival enhancement which led to a great controversy and debate over the use of bevacizumab. The discrepancy between PFS and overall survival also raises the question of whether or not bevacizumab has been applied sub-optimally in some of the studies, if a predictive biomarker(s) exists to select the group of patients whom would receive the greatest benefit and what is the appropriate clinical end-point for approval and funding of new targeted agents. In this article we will review the bevacizumab mechanism of action and the clinical trials that assessed its benefit in the treatment of metastatic breast cancer (MBC).     

How Should We Inform Women at Higher Risk of Breast Cancer About Tamoxifen? An Approach with a Decision Guide

Summary Background. Tamoxifen has been shown to reduce the incidence of invasive breast cancer in women at higher risk. Translating these research results to clinical practice is challenging. Our objective was to develop and evaluate a decision-making guide and process that can be used in clinical practice to inform eligible women of chemoprevention with tamoxifen. Methods. A decision guide explaining the benefits and risks of tamoxifen was developed with input from health care professionals and two focus groups of women both with and without cancer. Following consent, 51 eligible women presenting to a multi-disciplinary diagnostic facility for breast problems were given the decision guide/questionnaire to read, fill out and return by mail. Women with further questions or wanting to take tamoxifen were encouraged to re-contact their physicians. Results. Atypia was seen in 60% of subjects. Median 5-year Gail risk was 3.7 (range 1.7–9.4). Only 6 (11.8% 95% CI = 2.9, 20.6%) women reported they would like to take tamoxifen while 6 (11.8% 95% CI = 2.9, 20.6%) remained uncertain. Conclusion. We have developed a decision-making guide and process that is acceptable to providers and women to identify and inform women at higher risk of breast cancer with regard to chemoprevention with tamoxifen. Few women in this select group, when provided with a balanced decision guide, wished to pursue chemoprevention with tamoxifesn