PURPOSE Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (g BRCA-positive) and operable breast cancer. METHODS Eligibility included 1 cm or larger invasive tumor and g BRCA-positive disease. Human epidermal growth factor receptor 2–positive tumors were excluded. Twenty patients underwent a pretreatment biopsy, 6 months of once per day oral talazoparib (1 mg), followed by definitive surgery. Patients received adjuvant therapy at physician’s discretion. The primary end point was residual cancer burden (RCB). With 20 patients, the RCB-0 plus RCB-I response rate can be estimated with a 95% CI with half width less than 20%. RESULTS Twenty patients were enrolled from August 2016 to September 2017. Median age was 38 years (range, 23 to 58 years); 16 patients were g BRCA1 positive and 4 patients were g BRCA2 positive. Fifteen patients had triple-negative breast cancer (estrogen receptor/progesterone receptor < 10%), and five had hormone receptor-positive disease. Five patients had clinical stage I disease, 12 had stage II, and three had stage III, including one patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma. One patient chose to receive chemotherapy before surgery and was not included in RCB analyses. RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%. Eight patients (40%) had grade 3 anemia and required a transfusion, three patients had grade 3 neutropenia, and 1 patient had grade 4 thrombocytopenia. Common grade 1 or 2 toxicities were nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea. Toxicities were managed by dose reduction and transfusions. Nine patients required dose reduction. CONCLUSION Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports the larger, ongoing neoadjuvant trial (ClinicalTrials.gov identifier: NCT03499353 ).

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Purpose To determine the relationship of microcalcification morphology and distribution with clinical, histopathologic, biologic features and local recurrence (LR) in patients with pure ductal carcinoma in situ (DCIS) of the breast. Methods All patients with pure DCIS who underwent preoperative mammography at our institution from 1996 through 2009 were identified. Mammographic findings were classified according to the ACR BI-RADS lexicon. Associations between mammographic findings and clinical, histopathologic, biologic characteristics and LR were analyzed. Statistical inference used multiple logistic regression and Cox proportional hazards regression adjusted for age and confounding due to bias from nonrandomized selection of radiation therapy. Results We identified 1657 patients with microcalcifications visualized on mammography. The mean age at diagnosis was 55 years (SD, 11). The mean follow-up was 7 years (range, 1–16). Ipsilateral LR was 4% in segmentectomy (987) and 1.5% in mastectomy (670) patients. Increased LR risk was seen in patients with dense breast tissue (p<0.05) and larger DCIS size (p<0.01). Radiation therapy was associated with a 2.8-fold decrease in the LR risk. Fine linear (branching) microcalcifications were associated with 5.2-fold increase in LR. Extremely dense breast tissue was associated with positive/close margins (p=0.04) and multicentricity (p<0.01). Younger women were more likely to have extremely dense breast tissue (p<0.0001), multicentric disease (p<0.0004), and undergo mastectomy (p<0.0001). Conclusions Dense breast tissue, large DCIS size, and fine linear (branching) microcalcifications were associated with increased LR, yet overall LR rates remained low. Extremely dense breast tissue was a risk factor for multicentricity and positive margins in DCIS.

Background The clinicopathologic, mammographic, and sonographic findings in patients with pure ductal carcinoma in situ (DCIS) were assessed by estrogen receptor (ER) expression. Methods After institutional review board approval, patients with pure DCIS evaluated from January 1996 to July 2009 with known ER status and available imaging were identified. Images were reviewed per the ACR BI-RADS® lexicon (4th edition). Clinical, pathologic, and imaging characteristics were analyzed by ER status using t-test, chi-square test, and Fisher’s exact test. Results Of 1219 patients with pure DCIS and known ER status identified, 1187 with complete data were included. Mammography was performed in all 1187 patients and sonography in 519 (44%). There were 972 (82%) patients with ER-positive and 215 (18%) with ER-negative disease. ER-negative DCIS was more likely to be high grade (93% vs 44%, p<0.0001), associated with comedonecrosis (64% vs 29%, p<0.0001), and multifocal (23% vs 15%, p=0.009). On sonography, ER-negative DCIS was more likely to be visible (61% vs 46%, p=0.004), larger (mean size, 2.3 vs 1.6 cm, p=0.006), and show posterior shadowing (53% vs 28%, p=0.006). Mastectomy was more frequently performed for ER-negative DCIS (47% vs 37%, p=0.008). Palpable DCIS was visible on sonography in 55% of cases and mammography in 81%. Compared with ER-positive palpable DCIS, ER-negative palpable DCIS was larger and more likely to be visible on sonography. Compared with ER-positive noncalcified DCIS, ER-negative noncalcified DCIS was less likely to be visible on mammography. Conclusion ER-positive and ER-negative pure DCIS have different clinicopathologic and imaging characteristics. ER-negative DCIS is associated with worse prognostic factors then ER-positive DCIS. On sonography, ER-negative DCIS is more frequently visible than ER-positive DCIS, tends to be larger, and more frequently demonstrates posterior shadowing.

Of the 691 pure DCIS lesions, 362 (52%) were visible on sonography and presented most commonly as a mass. Lesion visibility of DCIS on sonography was not related to nuclear grade or the presence of comedonecrosis.

This study was undertaken to determine the feasibility of enrolling breast cancer patients on a single-agent-targeted therapy trial before neoadjuvant chemotherapy. Specifically, we evaluated talazoparib in patients harboring a deleterious BRCA mutation (BRCA+). Patients with a germline BRCA mutation and ≥1 cm, HER2-negative primary tumors were eligible. Study participants underwent a pretreatment biopsy, 2 months of talazoparib, off-study core biopsy, anthracycline, and taxane-based chemotherapy ± carboplatin, followed by surgery. Volumetric changes in tumor size were determined by ultrasound at 1 and 2 months of therapy. Success was defined as 20 patients accrued within 2 years and <33% experienced a grade 4 toxicity. The study was stopped early after 13 patients (BRCA1 + n = 10; BRCA2 + n = 3) were accrued within 8 months with no grade 4 toxicities and only one patient requiring dose reduction due to grade 3 neutropenia. The median age was 40 years (range 25–55) and clinical stage included I (n = 2), II (n = 9), and III (n = 2). Most tumors (n = 9) were hormone receptor-negative, and one of these was metaplastic. Decreases in tumor volume occurred in all patients following 2 months of talazoparib; the median was 88% (range 30–98%). Common toxicities were neutropenia, anemia, thrombocytopenia, nausea, dizziness, and fatigue. Single-agent-targeted therapy trials are feasible in BRCA+ patients. Given the rapid rate of accrual, profound response and favorable toxicity profile, the feasibility study was modified into a phase II study to determine pathologic complete response rates after 4–6 months of single-agent talazoparib.

Short-protocol breast MRI comprising a T2-weighted sequence and a fast dynamic sequence with less than 10-minute acquisition time is feasible and has image quality at least equivalent to that of an SOC MRI protocol with a > 20-minute mean acquisition time. Larger studies comparing the cancer detection rate, sensitivity, and specificity of each imaging protocol are needed to determine whether short-protocol breast MRI can replace SOC MRI to screen patients at high breast cancer risk.