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After completing this CME activity, physicians should be better able to assess the effect pregnancy has on long-term survival in primary breast cancer patients under age 45; counsel patients on the safety of pregnancy after breast cancer diagnosis and treatment; and interpret how pregnancy may be associated with improved breast cancer survival.

To address whether the use of bisphosphonates in the adjuvant setting of breast cancer might have any effect on the natural course of the disease, a meta-analysis was conducted of published and unpublished randomized controlled trials found in PubMed, the Cochrane Central Register of Controlled Trials, the ISI Web of Knowledge, and abstracts of major international conferences up to January 2009. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with any bisphosphonate versus non-use were considered eligible. Analysis included data from 13 eligible trials involving 6886 patients randomized to treatment with bisphosphonates (n = 3414) or either placebo or no treatment (n = 3472). Compared with no use, adjuvant breast cancer treatment with bisphosphonates did not reduce the overall number of deaths (odds ratio [OR], 0.708; 95% CI, 0.482-1.041; P = .079), bone metastases (OR, 0.925; 95% CI, 0.768-1.114; P = .413), overall disease recurrences (OR, 0.843; 95% CI, 0.602-1.181; P = .321), distant relapse (OR, 0.896; 95% CI, 0.674-1.192; P = .453), visceral recurrences (OR, 1.051; 95% CI, 0.686-1.609; P = .820), or local relapses (OR, 1.056; 95% CI, 0.750-1.487; P = .756). No significant heterogeneity was observed among the trials except for estimates of deaths and disease recurrences (P = .034 and P = .016, respectively). In subgroup analyses, use of zoledronic acid was associated with a statistically significant lower risk for disease recurrence (OR, 0.675; 95% CI, 0.479-0.952; P = .025). However, these results should be interpreted with caution because the statistical significance for this association was weak and might be attributed to chance from multi-test analyses. Use of zoledronic acid was not associated with any significant difference in death (OR, 0.642; 95% CI, 0.388-1.063) and bone metastasis rates (OR, 0.661; 95% CI, 0.379-1.151). Currently available evidence does not support the hypothesis that use of bisphosphonates in adjuvant treatment of early breast cancer will alter the natural course of the disease. Nonetheless, a nonsignificant trend seems to exist for better outcomes in patients undergoing bisphosphonate treatment. Until further evidence from new clinical trials becomes available, adjuvant bisphosphonates should not be recommended routinely.

Treatment of unexplained infertility is empiric and different regimens or protocols have been used so far. Clomiphene can be used alone or combined with gonadotrophins. Aromatase inhibitors may offer an alternative for first-line treatment. To compare the efficacy of aromatase inhibitors versus climiphene, we conducted a systematic review and meta-analysis for randomized controlled trials comparing the above regimens to estimate live pregnancy rates in women with unexplained infertility. Trials were located through PubMed and Cochrane Library searches. Methodological quality of included trials has been assessed. Then, 2 x 2 tables were constructed, and pooled odds ratios (ORs) were calculated. Ten arms (273 patients) were included in the meta-analysis. ORs were homogeneous between studies (heterogeneity chi2 = 2.33, P = 0.676). No difference was observed for live pregnancies (pooled OR 0.87, 95% CI, 0.46-1.65, P = 0.666) for aromatase inhibitors versus clomiphene citrate; however, the definition of live pregnancy by the authors was clear only in one trial. Data regarding secondary outcomes were omitted, and methodogical quality of eligible trials did not reach high scores. Evidence from randomized data regarding the use of aromatase inhibitors is fragmented and weak. Aromatase inhibitors may have a role in the treatment of women with unexplained infertility desiring pregnancy. However, meticulous reporting and study design should be a priority in this field and large, registered, and properly designed randomized trials are essential to test whether aromatase inhibitors can be introduced as a first-line treatment in carefully selected subgroups of women with unexplained infertility.

As the incidence of malignancies in young adults is increasing, fertility preservation in cancer survivors arises as a major concern. Especially among female cancer patients, pregnancy rates are estimated to be 40% lower compared to women of the same age. Nowadays oncologists are to be preoccupied not only with their patients’ successful treatment, but also with the maintenance of the potential of the latter to conceive and obtain children. Chemotherapy associated ovarian failure (COF), refers to disruption of ovarian function both as an endocrine gland and as a reproductive organ, due to previous exposure to chemotherapy agents. Although the underlying mechanism is not fully understood, it is supposed that chemotherapy agents may induce either DNA damage of premature ovarian follicle or early activation and apoptosis of them, resulting into early exhaustion of available follicle deposit. Various chemotherapy agents have been associated with COF with the highest incidence being reported for patients undergoing combination regimens. Although a variety of alternatives in order to maintain ovarian function and fertility in female cancer survivors are available, adequately established practices to do so are lacking. Thus, it is of major importance to investigate further and collect sufficient evidence, aiming to guide patients and physicians in everyday clinical practice.

Cancer cachexia global awareness appears extremely low; guideline implementation on the web was inconsistent for any category analysed (nation vs continent vs international vs society type vs physician vs patient oriented) and for updating.

Surgical resection is the only option of cure for patients with metastatic colorectal cancer. Risk of recurrence after metastasectomy is around 75%. Use of adjuvant chemotherapy after metastasectomy is controversial.AimTo address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone.MethodsSystematic review of literature and meta-analysis of all available randomised evidence. Relative hazards (RHs) were summarised across trials and heterogeneity was assessed with the Q and I2 statistics.ResultsFive trials were eligible. Three trials, all using single-agent fluoropyrimidine chemotherapy, presented data valuable for analyses. 482 patients were included in the meta-analysis: 238 randomly assigned to receive postoperative chemotherapy and 244 to metastasectomy only. We found no overall survival (OS) benefit with the use of postoperative single-agent fluoropyrimidines compared with surgery alone, even if a trend for benefit was observed (relative hazard (RH)=0.781, 95% CI 0.593 to 1.030, p=0.080). Significant disease-free survival benefit with the use of postoperative chemotherapy was observed (RH=0.645, 95% CI 0.509 to 0.818, p=0.001). No quality of life (QL) data were available. All trials showed accrual delay, two stopped and one recruiting after 10 years. Long follow-up needs were evidenced since OS curves split only after 3.5 years.ConclusionsNo OS benefit was documented from the use of postoperative monochemotherapy. Metastasectomy alone continues to be the standard of care. Combination chemotherapy regimens should be evaluated along with QL assessment in future trials appropriately designed for long-term accrual and follow-up.

Background: The number of genetic association studies is increasing exponentially. Nonetheless, genetic association reports are prone to potential biases which may influence the reported outcome.Aim: We hypothesized that positive outcome for a determined polymorphism might be over-reported across genetic association studies analysing a small number of polymorphisms, when compared to studies analysing the same polymorphism together with a high number of other polymorphisms.Methods: We systematically reviewed published reports on the association of glutathione s-transferase (GST) single-nucleotide polymorphisms (SNPs) and cancer outcome.Result: We identified 79 eligible trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies analysing one to three polymorphisms (n = 39) were significantly more likely to present positive outcomes, compared to studies examining more than 3 polymorphisms (n=40) p = 0.004; this was particularly evident for studies analysing the GSTM1polymorphism (p =0.001). We found no significant associations between journal impact factor, number of citations, and probability of publishing positive studies or studies with 1-3 polymorphisms examined.Conclusions: We propose a new subtype of publication bias in genetic association studies. Positive results for genetic association studies analysing a small number of polymorphisms (n = 1-3) should be evaluated extremely cautiously, because a very large number of such studies are inconclusive and statistically under-powered. Indeed, publication of misleading reports may affect harmfully medical decision-making and use of resources, both in clinical and pharmacological development setting.