Rassegna della letteratura – aprile 2019

Epidemiologia, prevenzione, diagnosi e screening

Khan KA, Mazuquin B – Systematic review of economic evaluations of exercise and physiotherapy for patients treated for breast cancer. – Breast Cancer Res Treat. 2019 Apr 17. doi: 10.1007/s10549-019-05235-7.

Background: Treatments for breast cancer can lead to chronic musculoskeletal problems. This study aimed to systematically review the evidence surrounding the cost-effectiveness of exercise and physiotherapy interventions aimed at reducing the risk of physical symptoms and functional limitations due to breast cancer treatment.

Methods: A systematic review of the cost-effectiveness of exercise and physiotherapy interventions during and following treatment for breast cancer was undertaken according to PRISMA guidelines. Literature searches were carried out in Ovid MEDLINE, Ovid Embase, Web of Science, EconLit, CINAHL, PsycINFO, Scopus and the Cochrane Library. Cost-effectiveness evidence was summarised in a descriptive manner and studies were assessed using quality appraisal tools. The review protocol was registered on PROSPERO

Results: A total of 7783 articles were identified and seven were included in the final review. Five studies undertook trial-based economic evaluations, whereas two studies conducted economic evaluation based on decision models. One study was a cost-effectiveness analysis (CEA), three undertook stand-alone cost-utility analyses (CUA) and three studies were combined CEAs and CUAs. Three studies reported favourable cost-effectiveness results for different exercise or physiotherapy interventions. In contrast, four studies found that exercise and physiotherapy interventions were not cost-effective on the basis of quality-adjusted life year outcomes.

Conclusions: The evidence surrounding the cost-effectiveness of exercise and physiotherapy interventions for the treatment of breast cancer remains sparse with contrasting conclusions. Future research should particularly aim to broaden the evidence base by disentangling the contributing effects of frequency, intensity, time and type of exercise and physiotherapy interventions on cost-effectiveness outcomes.


Shimada S, Yoshida R et Al. – Five screening-detected breast cancer cases in initially disease-free BRCA1 or BRCA2 mutation carriers. – Breast Cancer. 2019 Apr 12. doi: 10.1007/s12282.

Background: Individuals carrying pathogenic BRCA1 or BRCA2 mutations have an increased lifetime risk of breast and/or ovarian cancer. The incidence of breast cancer amongst disease-free BRCA mutation carriers under surveillance and the clinical and pathological characteristics of those who subsequently develop the disease remain unclear in Japan. We reviewed the records of 155 individuals with BRCA1 or BRCA2 mutations identified by genetic testing between January 2000 and December 2016. At the time of genetic testing, 26 individuals with one of these mutations had no history of breast cancer and were therefore enrolled in a surveillance program that included biannual ultrasonography, clinical breast examination, annual mammography, and conditional magnetic resonance imaging for the early detection of primary breast cancer. During the surveillance period, 5 individuals with BRCA1 or BRCA2 mutations were diagnosed with primary breast cancer. The mean surveillance duration until breast cancer diagnosis was 48 months. The incidence of primary breast cancer during surveillance in initially disease-free BRCA mutation carriers was 4.23%/year. In two cases, the tumors were only detectable on MRI. The case 5 patient who presented with a tumor that was detected by self-examination, which then grew rapidly, had stage IIB triple-negative breast cancer. In conclusion, our results show that some challenges exist in the early detection of breast cancers in BRCA1 or BRCA2 mutation carriers. There are also some difficulties in approaching those individuals in Japanese society.

Malmartel A, Tron A et Al. – Accuracy of clinical breast examination’s abnormalities for breast cancer screening: cross-sectional study. – Eur J Obstet Gynecol Reprod Biol. 2019 Apr 3;237:1-6. doi: 10.1016/j.ejogrb.2019.04.003.

Background: The guidelines for breast cancer screening with clinical breast examination (CBE) are diverging CBE is recommended in France, whereas it is not recommended in the United States and Canada, given the lack of clear benefit and the risk of overmedication. To assess the accuracy of abnormalities found during CBE for in breast cancer screening

Methods: A cross-sectional study included women over 18 years with no history of breast cancer coming for a mammography at 3 ambulatory radiology practices in Paris. A questionnaire collected the risk of breast cancer on mammography according to the Breast Imaging-Reporting And Data System (Bi-RADS) (high risk: Bi-RADS 4 or 5 versus lower risk: other Bi-RADS categories), the risk factors for breast cancer and the breast clinical abnormalities (none, mass, skin abnormality, oedema, pain, nipple discharge, lymph nodes…) For each abnormality, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated.

Results: Among the 3218 included patients (mean age 55.1 +/-10 years), 713 (22.2%) had an abnormal CBE and 133 (4.1%) had high-risk mammography. The sensitivity of CBE was 36%[28%;45%] and the specificity was 78%[77%;80%]. The PPV and NPV for each clinical abnormality were low, except for nipple discharge, retraction and lymph nodes, for which the PPV were 10.5[3.7;29.9], 6.6[1.4;31.6], and 5.0[1.5;17.1], respectively, but these abnormalities were rare (0.5%, 0.2% and 0.5% respectively). These values were similar across all age groups.

Conclusions: The accuracy of CBE for breast cancer screening appeared to be low which did not support recommending regular CBE in France.

DeCensi A, Puntoni M et AL. – Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. – J Clin Oncol. 2019 Apr 11:JCO1801779. doi: 10.1200/JCO.18.01779.

Background: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose.

Methods: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ.

Results: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo.

Conclusions: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.