Rassegna della letteratura – aprile/giugno 2020
Epidemiologia, prevenzione, diagnosi e screening
Breast cancer prevention in high-risk women. Mangesh A Thorat, Rajeshkumar Balasubramanian – Best Pract Res Clin Obstet Gynaecol 2020 May;65:18-31.
Women at high risk of developing breast cancer are a heterogeneous group of women including those with and without high-risk germline mutation/s. Prevention in these women requires a personalised and multidisciplinary approach. Preventive therapy with selective oestrogen receptor modulators (SERMs) like tamoxifen and aromatase inhibitors (AIs) substantially reduces breast cancer risk well beyond the active treatment period. The importance of benign breast disease as a marker of increased breast cancer risk remains underappreciated, and although the benefit of preventive therapy may be greater in such women, preventive therapy remains underutilised in these and other high-risk women. Bilateral Risk-Reducing Mastectomy (BRRM) reduces the risk of developing breast cancer by 90% in high-risk women such as carriers of BRCA mutations. It also improves breast cancer-specific survival in BRCA1 carriers. Bilateral risk-reducing salpingo-oophorectomy may also reduce risk in premenopausal BRCA2 carriers. Further research to improve risk models, to identify surrogate biomarkers of preventive therapy benefit and to develop newer preventive agents is needed.
Fast MRI breast cancer screening – Ready for prime time. Sasan Partovi , David Sin et Al.- Clin Imaging . 2020 Apr;60(2):160-168.
Objective: The manuscript discusses landmark studies using abbreviated MRI for breast cancer screening. This includes abbreviated dynamic contrast enhanced MRI and diffusion weighted imaging. Our institutional experience with abbreviated MR protocol for breast cancer screening is also described.
Conclusion: Abbreviated MRI protocols were found to demonstrate value for screening of breast cancer. It has been shown that abbreviated protocol MRI provides similar diagnostic sensitivities to full protocol MRI for breast cancer in women with increased lifetime risk. Our institutional abbreviated MRI protocol for breast cancer offers improved time and workflow efficiencies and has the potential to increase the number of breast cancers detected and the detection of pathologically relevant invasive breast cancer at earlier stages.
Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. D Huber , S Seitz , G Emons et Al. / Arch Gynecol Obstet . 2020 Apr;301(4):875-884.
Purpose: BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers.
Methods: We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library.
Results: We included four meta-analyses, one review, one case-control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case-control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC.
Conclusion: Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.
Invasive breast cancer and breast cancer mortality after ductal carcinoma in situ in women attending for breast screening in England, 1988-2014: population based observational cohort study. Gurdeep S Mannu , Zhe Wang , John Broggio / BMJ. 2020 May 27;369:m1570.
Objective: To evaluate the long term risks of invasive breast cancer and death from breast cancer after ductal carcinoma in situ (DCIS) diagnosed through breast screening.
Design: Population based observational cohort study.
Setting: Data from the NHS Breast Screening Programme and the National Cancer Registration and Analysis Service.
Participants: All 35 024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014.
Main outcome measures: Incident invasive breast cancer and death from breast cancer.
Results: By December 2014, 13 606 women had been followed for up to five years, 10 998 for five to nine years, 6861 for 10-14 years, 2620 for 15-19 years, and 939 for at least 20 years. Among these women, 2076 developed invasive breast cancer, corresponding to an incidence rate of 8.82 (95% confidence interval 8.45 to 9.21) per 1000 women per year and more than double that expected from national cancer incidence rates (ratio of observed rate to expected rate 2.52, 95% confidence interval 2.41 to 2.63). The increase started in the second year after diagnosis of DCIS and continued until the end of follow-up. In the same group of women, 310 died from breast cancer, corresponding to a death rate of 1.26 (1.13 to 1.41) per 1000 women per year and 70% higher than that expected from national breast cancer mortality rates (observed:expected ratio 1.70, 1.52 to 1.90). During the first five years after diagnosis of DCIS, the breast cancer death rate was similar to that expected from national mortality rates (observed:expected ratio 0.87, 0.69 to 1.10), but it then increased, with values of 1.98 (1.65 to 2.37), 2.99 (2.41 to 3.70), and 2.77 (2.01 to 3.80) in years five to nine, 10-14, and 15 or more after DCIS diagnosis. Among 29 044 women with unilateral DCIS undergoing surgery, those who had more intensive treatment (mastectomy, radiotherapy for women who had breast conserving surgery, and endocrine treatment in oestrogen receptor positive disease) and those with larger final surgical margins had lower rates of invasive breast cancer.
Conclusions: To date, women with DCIS detected by screening have, on average, experienced higher long term risks of invasive breast cancer and death from breast cancer than women in the general population during a period of at least two decades after their diagnosis. More intensive treatment and larger final surgical margins were associated with lower risks of invasive breast cancer.
Digital breast tomosynthesis for breast cancer detection: a diagnostic test accuracy systematic review and meta-analysis Mostafa Alabousi , NanxiZha , Jean-Paul Salameh et Al. – Eur Radiol. 2020 Apr;30(4):2058-2071
Objectives: No consensus exists on digital breast tomosynthesis (DBT) utilization for breast cancer detection. We performed a diagnostic test accuracy systematic review and meta-analysis comparing DBT, combined DBT and digital mammography (DM), and DM alone for breast cancer detection in average-risk women.
Methods: MEDLINE and EMBASE were searched until September 2018. Comparative design studies reporting on the diagnostic accuracy of DBT and/or DM for breast cancer detection were included. Demographic, methodologic, and diagnostic accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Accuracy metrics were pooled using bivariate random-effects meta-analysis. The impact of multiple covariates was assessed using meta-regression.
Results: Thirty-eight studies reporting on 488,099 patients (13,923 with breast cancer) were included. Eleven studies were at low risk of bias. DBT alone, combined DBT and DM, and DM alone demonstrated sensitivities of 88% (95% confidence interval [CI] 83-92), 88% (CI 83-92), and 79% (CI 75-82), as well as specificities of 84% (CI 76-89), 81% (CI 73-88), and 79% (CI 71-85), respectively. The greater sensitivities of DBT alone and combined DBT and DM compared to DM alone were preserved in the combined meta-regression models accounting for other covariates (p = 0.003-0.006). No significant difference in diagnostic accuracy between DBT alone and combined DBT and DM was identified (p = 0.175-0.581).
Conclusions: DBT is more sensitive than DM, while the addition of DM to DBT provides no additional diagnostic benefit. Consideration of these findings in breast cancer imaging guidelines is recommended.
Effect of screening mammography on breast cancer mortality: Quasi-experimental evidence from rollout of the Dutch population-based program with 17-year follow-up of a cohort. Tom Van Ourti , Owen O’Donnell , Hale Koç et Al./ Int J Cancer . 2020 Apr 15;146(8):2201-2208.
There is uncertainty about the magnitude of the effect of screening mammography on breast cancer mortality. The relevance and validity of evidence from dated randomized controlled trials has been questioned, whereas observational studies often lack a valid comparison group. There is no estimate of the effect of one screening invitation only. We exploited the geographic rollout of the Dutch screening mammography program across municipalities to estimate the effects of one additional biennial screening invitation on breast cancer and all-cause mortality. Population administrative data provided vital status and cause of death of a cohort of women aged 49-63 in 1995 over 17 years. Linear probability models were used to estimate the mortality effects. We estimated 154 fewer breast cancer deaths (95% confidence interval: 40-267; p = 0.01) over 17 years in a population of 100,000 women aged 49-63 who received one additional biennial screening invitation, which corresponds to an 9.6% risk reduction for a woman of age 56. The estimated effect on all-cause mortality was negative but not close to statistical significance. Our study shows that one single invitation for breast cancer screening is effective in reducing breast cancer mortality, which is important for health policy. The effect is smaller than previous estimates of the effect of invitation for multiple screens, which further emphasizes the importance of achieving regular participation.
Analysis of breast cancer cases according to county-level poverty status in 3.5 million rural women who participated in a breast cancer screening program of Hunan province, China from 2016 to 2018. Xiong Lili , Liu Zhiyu , Wu Yinglan et AL./ Medicine (Baltimore) . 2020 Apr;99(17):e19954.
The Hunan provincial government has implemented a free breast cancer screening program for rural women aged 35 to 64 years from 2016, under a 2015 policy aimed at of poverty eradication and improving women’s health in China. However, there has been no population study of the breast cancer screening program in China to date, especially considering exploring differences related to the area’s poverty status. We explored differences in risk factors, clinical examination results, and clinicopathological features among breast cancer patients in poor compared with non-poor counties in rural areas of Hunan province from 2016 to 2018 using χ and Fisher’s exact test, and multivariate logistic regression analysis. A total of 3,151,679 women from rural areas participated in the screening program, and the breast cancer prevalence was 37.09/10. Breast cancer prevalence was lower in poor (29.68/10) than in non-poor counties (43.13/10). There were differences between breast cancers in poor and non-poor counties in terms of cysts, margins, internal echo, blood flow in solid masses in the right breast on ultrasound examination, lump structure in mammograms, and clinicopathological staging and grading in pathological examinations. Breast cancer in poor counties was more likely to be diagnosed at later stages as determined by ultrasound, mammography, and pathological examinations. Furthermore, indexes of the breast screening program including early detection, prevalence, pathological examination, and mammography examination were lower in poor compared with non-poor counties. Multivariate logistic regression analysis showed that education, ethnicity, reproductive history and the year 2017 were associated with an increased risk of breast cancer in poor counties (odds ratio >1, P < .05). In conclusion, women in poor areas were more likely to be diagnosed with breast cancer at a later stage compared with women in non-poor areas. Women in poor areas of Hunan province should therefore have better access to diagnostic and clinical services to help rectify this situation.
Associations of aspirin and other anti-inflammatory medications with mammographic breast density and breast cancer risk. Lusine Yaghjyan, Akemi Wijayabahu , A Heather Eliassen et Al / Cancer Causes Control . 2020 Sep;31(9):827-837.
Purpose: We investigated the associations of aspirin and other non-steroid anti-inflammatory drugs with mammographic breast density (MBD) and their interactions in relation to breast cancer risk.
Methods: This study included 3,675 cancer-free women within the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) cohorts. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Information on medication use was collected in 1980 (NHS) and 1989 (NHSII) and updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users from all bi-annual questionnaires preceding the mammogram date. We used generalized linear regression to quantify associations of medications with MBD. Two-way interactions were examined in logistic regression models.
Results: In multivariate analysis, none of the anti-inflammatory medications were associated with PD, DA, and NDA. We found no interactions of any of the medications with PD with respect to breast cancer risk (all p-interactions > 0.05). However, some of the aspirin variables appeared to have positive associations with breast cancer risk limited only to women with PD 10-24% (past aspirin OR 1.56, 95% CI 1.03-2.35; current aspirin with < 5 years of use OR 1.82, 95% CI 1.01-3.28; current aspirin with ≥ 5 years of use OR 1.89, 95% CI 1.26-2.82).
Conclusions: Aspirin and NSAIDs are not associated with breast density measures. We found no interactions of aspirin with MBD in relation to breast cancer risk.