Breast cancer is the most common cancer among women worldwide, and survival rates are increasing. Chemotherapy-associated peripheral neuropathy (PN) is clinically important because of effects on quality of life (QOL) and potential effects on dose limitations. This adverse drug reaction is associated with certain classes of chemotherapy and commonly presents as peripheral sensory neuropathy whose natural course is largely unknown. The literature was reviewed to determine the frequency and characteristics of PN associated with adjuvant chemotherapy in early-stage breast cancer (ESBC) to explore the potential impact on long-term (one or more years after diagnosis) health outcomes and QOL. MEDLINE, PubMed, Embase, and the Cochrane Library were searched for relevant English-language randomized controlled trials, systematic reviews, meta-analyses, and case-control and cohort studies published between January 1990 and July 1996. Included studies were limited to current adjuvant regimens (eg, anthracyclines, taxanes, cyclophosphamide, platinum compounds). Two investigators independently reviewed abstracts, full-text articles, and extracted data from fair- and good-quality studies. Discrepancies in quality assessment and data extraction were resolved by consensus. We identified 364 articles; 60 were eligible for full-text review. Only five reports of four studies provided data beyond one year post-treatment initiation. Studies used different measures to assess PN. Neuropathic symptoms persisted in 11.0% to more than 80% of participants at one to three years following treatment. There is a paucity of data describing persistent PN in ESBC patients. Consistent use of validated measures and well-conducted randomized clinical trials or observational studies are needed to evaluate the incidence, persistence, and QOL associated with the long-term effects of PN.

Background

Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk.

Purpose

To perform a systematic review of reproducibility of Breast Imaging Reporting and Data System (BI-RADS) density categorization and test performance and clinical outcomes of supplemental screening with breast ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT) in women with dense breasts and negative mammography results.

Data sources

MEDLINE, PubMed, EMBASE, and Cochrane database from January 2000 to July 2015.

Study selection

Studies reporting BI-RADS density reproducibility or supplemental screening results for women with dense breasts.

Data extraction

Quality assessment and abstraction of 24 studies from 7 countries; 6 studies were good-quality.

Data synthesis

Three good-quality studies reported reproducibility of BI-RADS density; 13% to 19% of women were recategorized between "dense" and "nondense" at subsequent screening. Two good-quality studies reported that sensitivity of ultrasonography for women with negative mammography results ranged from 80% to 83%; specificity, from 86% to 94%; and positive predictive value (PPV), from 3% to 8%. The sensitivity of MRI ranged from 75% to 100%; specificity, from 78% to 94%; and PPV, from 3% to 33% (3 studies). Rates of additional cancer detection with ultrasonography were 4.4 per 1000 examinations (89% to 93% invasive); recall rates were 14%. Use of MRI detected 3.5 to 28.6 additional cancer cases per 1000 examinations (34% to 86% invasive); recall rates were 12% to 24%. Rates of cancer detection with DBT increased by 1.4 to 2.5 per 1000 examinations compared with mammography alone (3 studies). Recall rates ranged from 7% to 11%, compared with 7% to 17% with mammography alone. No studies examined breast cancer outcomes.

Limitations

Good-quality evidence was sparse. Studies were small and CIs were wide. Definitions of recall were absent or inconsistent.

Conclusion

Density ratings may be recategorized on serial screening mammography. Supplemental screening of women with dense breasts finds additional breast cancer but increases false-positive results. Use of DBT may reduce recall rates. Effects of supplemental screening on breast cancer outcomes remain unclear.

Primary funding source

Agency for Healthcare Research and Quality.