Treatment of ductal carcinoma in situ (DCIS) is controversial given the variable recurrence and progression to invasive carcinoma. Identifying women who would benefit from adjuvant radiation therapy on the basis of their recurrence risk may allow more individualized management strategies. The Oncotype DX Breast DCIS Score-which we refer to here as the "DCIS score"-is a validated surrogate marker of local recurrence. This study evaluated the association between BI-RADS mammographic calcification descriptors and the DCIS score.Fifty-eight women diagnosed with DCIS presenting with calcifications who had Oncotype DX Breast DCIS assay results were identified. Pretreatment BI-RADS mammographic calcification features were collected including morphology, distribution, and maximum span. The association between calcification descriptors and DCIS score was assessed with logistic regression modeling. Mean DCIS scores were calculated for calcification features significantly associated with DCIS score. All analyses were adjusted for patient age, DCIS grade, and progesterone receptor status.Of the suspicious calcifications that proved to represent DCIS, 19.0% were amorphous; 25.9%, coarse heterogeneous; 39.7%, fine pleomorphic; and 15.5%, fine linear or fine linear branching in morphology. The mean DCIS scores by calcification morphology were 22.3, 35.5, 36.7, and 44.1, respectively. Amorphous calcification morphology had a significantly lower adjusted mean DCIS score compared with fine pleomorphic morphology (p = 0.01) and fine linear or fine linear branching morphology (p = 0.02). The adjusted odds ratio (OR) of intermediate or high risk of recurrence (defined as a DCIS score ≥ 39) was significantly higher for women with fine pleomorphic calcifications (OR = 53.1, p = 0.01) and for those with fine linear or fine linear branching calcifications (OR = 24.0, p = 0.04) than for women with amorphous calcifications.Women with amorphous calcification morphology had the lowest DCIS scores compared with women with fine pleomorphic and fine linear or fine linear branching morphologies. Both fine pleomorphic and fine linear or fine linear branching morphologies were associated with higher odds of intermediate or high risk of recurrence. These findings suggest mammographic features are potential biomarkers of DCIS recurrence and could help individualize treatment decisions.
CALGB 40903 (Alliance) was a phase II single arm multicenter trial conducted in postmenopausal patients diagnosed with estrogen-receptor (ER) positive breast ductal carcinoma in situ (DCIS) without invasion. Patients were treated with the aromatase inhibitor (AI) letrozole for 6 months prior to surgery with change in magnetic resonance imaging (MRI) enhancement volume compared to baseline as the primary endpoint. In the current study, we performed sequence analysis of pre- and post-treatment specimens to determine gene expression and DNA copy number parameters associated with treatment and response. Paraffin sections from pretreatment biopsies and post-treatment surgical specimens were evaluated for presence of DCIS. Proliferation based on KI67 staining was quantified by a study pathologist. Macrodissection of the DCIS components from thin sections was the source of RNA and DNA. Whole-transcriptome RNA and shallow whole-genome DNA sequencing were performed. PAM50 analysis to assign intrinsic subtypes with associated probability of class membership was performed. Differential gene expression comparing responders versus non-responders and pre- versus post-treatment specimens was performed using a two-tiered approach based on candidate genes and a whole genome survey with appropriate multiple testing corrections. Based on availability of specimens and presence of DCIS component, 29 patients (from the 70 who completed the treatment trial) were included in the final data set, including five who had a pathologic complete response (pCR). Response to treatment was qualified categorically based on a threshold of 10% KI67 in the post-treatment surgical specimen or pCR. Based on this criterion, six of the 29 DCIS were considered non-responders (> 10% KI67) and five subjects with pCR were assigned to the responder group. No standard clinical variables were associated with response. On the basis of gene expression analysis, 19 of the pre-treatment samples were classified as luminal A, all of which were classified as responders. PAM50 classification of the other ten pre-treatment samples included luminal B, HER2, basal, and normal-like, six of which were non-responders. PAM50 class membership shifted from baseline to post-treatment in eight cases, most often from luminal A to normal-like (five cases). Selected genes associated with estrogen receptor levels in invasive breast cancer were higher in AI responsive tumors. AI treatment resulted in reductions in estrogen and proliferation related genes. Letrozole treatment produced an effective growth response, particularly in DCIS initially classified as luminal A. Study inclusion criteria of DCIS with at least 1% ER positive cells resulted in the inclusion of other subtypes that failed to respond. Treatment also induced both minor and major changes in intrinsic subtype based on PAM50 probabilities. Overall, these data indicate that response to AI treatment in ER( +) DCIS is variable and analogous to that observed in invasive breast cancers. Treatment for breast DCIS ranges from active surveillance to mastectomy, often combined with adjuvant endocrine therapy. The work presented here based on a unique neoadjuvant trial provides direct information on hormone therapy responsiveness of this disease and further couples the biology of invasive breast cancer to its non-obligate precursor. ClinicalTrials.gov Identifier: NCT01439711.
Utility of Diagnostic Mammography as the Primary Imaging Modality for Palpable Lumps in Women With Almost Entirely Fatty BreastsOlivia E. Linden1, Jessica H. Hayward2, Elissa R. Price2, Tatiana Kelil2, Bonnie N. Joe2 and Amie Y. Lee2Audio Available | Share Claim CREDIT
Abstract Objective To assess the utilization of patient navigators at breast imaging facilities across the United States. Methods An online survey was distributed to physician members of the Society of Breast Imaging. Questions encompassed use of patient navigators in breast imaging including: presence and qualifications, roles in patient care, perceived benefits, and barriers. Data were analyzed to identify the overall prevalence of patient navigators, their responsibilities and qualifications, and the impact on breast imaging centers. Results Three-hundred and eighty-five board-certified radiologists practicing in the United States completed the survey. The most common practice types were private practice (52%; 201/385) and academic (29%; 110/385). The majority (67%; 256/385) employed navigators, and the most common qualification was a registered nurse (78%; 200/256). Navigators were used for a variety of patient communication and care coordination roles, most commonly to provide educational resources (86%; 219/256), assist patients with scheduling appointments (80%; 205/256), explain the biopsy process (76%;195/256), and communicate biopsy results (64%). Nearly all (99%; 254/256) respondents ranked patient navigators as valuable to extremely valuable in improving patient care and indicated they would recommend implementation of a patient navigation program to other breast imaging practices. The most common barrier to employing a navigator was the financial cost. Conclusion Patient navigators have been widely adopted in breast imaging practices across the United States, with two-thirds of respondents reporting use of a navigator. Although navigator roles varied by practice, nearly all radiologists utilizing patient navigators found that they positively impact patient care and would recommend them to other breast imaging practices.
Abstract BACKGROUND: Reconstruction of partial lumpectomy defects with reduction mammaplasty techniques can improve aesthetic outcomes. However, the impact of the significant tissue rearrangement on post-operative mammographic findings and subsequent recommendations for biopsy has not been well-studied. METHODS: A retrospective review of 50 patients who underwent partial mastectomy with immediate oncoplastic reduction mammaplasty reconstruction from 2001 to 2008 was performed. Mammography reports at 6 months, 1 year, 2 years, and 3 years post-operatively were reviewed for Breast Imaging Reporting and Data System (BI-RADS) scores, predominant findings, and recommendations for subsequent imaging or biopsy. RESULTS: At six months post-operatively, 49 patients (98%) had benign findings of post-surgical changes, while one patient had microcalcifications and underwent subsequent surgical re-excision with residual DCIS on pathologic analysis. At one year, 94% of patients continued to have benign mammograms; of these mammograms, 94% reported only post-surgical scarring, while 6% described benign-appearing scattered or dystrophic calcifications. Of the three patients with suspicious mammograms at one year, all underwent core biopsies with benign results. At two years, rates of fat necrosis (2%) and scattered or dystrophic calcifications (10%) increased, though all mammographic findings were considered benign and none required additional imaging or biopsies. By three years post-operatively, an additional two patients (4%) developed suspicious findings and underwent biopsies confirming local recurrence (one invasive, one in situ). The remaining 96% continued to have benign mammographic findings and were subsequently followed with routine biannual mammographic surveillance. Overall, 88% of patients required no additional intervention in the three-year period following oncoplastic reduction mammaplasty. Of patients recommended for biopsy, malignancy was discovered in 50%, including two local recurrences (4% of total patients). This data is similar to a previously published large study (1841 women) of mammographic surveillance after partial mastectomy without oncoplastic reconstruction at our institution, which found a 6% malignancy rate at 5 years. CONCLUSIONS: Although substantial tissue rearrangement is performed at the time of oncoplastic reduction mammaplasty, our results demonstrate low rates of abnormal post-operative mammograms and subsequent biopsies over the first three years following the procedure. These findings support the use of oncoplastic reduction mammaplasty as a strategy for improving reconstructive outcomes in patients undergoing partial mastectomy. Citation Format: Anne Warren Peled, Merisa Piper, Laura J Esserman, Robert D Foster, Hani Sbitany, Elissa R Price. Mammographic changes after oncoplastic reduction mammoplasty [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-01-04.
This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.
