Factors associated with relapse-free survival after neoadjuvant chemotherapy for breast cancer at a safety net medical center.

BACKGROUND: This study was designed to assess prognostic factors associated with relapse-free survival (RFS) after neoadjuvant chemotherapy (NAC) for breast cancer. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all breast cancer patients treated with NAC from 2015 to 2018. All patients had pre-and post-NAC MRI. RESULTS: For 102 patients, median follow-up was 47.4 months, and the five-year RFS was 74%. The 41 (40%) patients who achieved pathologic complete response (pCR) after NAC had a significantly higher five-year RFS than the 61 not achieving pCR. For 31 patients with triple-negative cancers, the five-year RFS was significantly higher in those achieving pCR vs. no pCR. The 44 (43%) patients who achieved radiographic complete response (rCR) after NAC had similar five-year RFS to the 58 (57%) not achieving rCR. CONCLUSION: pCR, node-negativity after NAC, and triple-negative subtype were prognostic factors associated with relapse-free survival after NAC.

Breast Density Legislation Impact on Breast Cancer Screening and Risk Assessment.

OBJECTIVE: To evaluate breast density notification legislation (BDNL) on breast imaging practice patterns, risk assessment, and supplemental screening. METHODS: A 20-question anonymous web-based survey was administered to practicing Society of Breast Imaging radiologists in the U.S. between February and April 2021 regarding breast cancer risk assessment, supplemental screening, and density measurements. Results were compared between facilities with and without BDNL using the two-sided Fisher's exact test. RESULTS: One hundred and ninety-seven radiologists from 41 U.S. states, with (187/197, 95%) or without (10/197, 5%) BDNL, responded. Fifty-seven percent (113/197) performed breast cancer risk assessment, and 93% (183/197) offered supplemental screening for women with dense breasts. Between facilities with or without BDNL, there was no significant difference in whether risk assessment was (P = 0.19) or was not performed (P = 0.20). There was no significant difference in supplemental screening types (P > 0.05) between BDNL and non-BDNL facilities. Thirty-five percent (69/197) of facilities offered no supplemental screening studies, and 25% (49/197) had no future plans to offer supplemental screening. A statistically significant greater proportion of non-BDNL facilities offered no supplemental screening (P < 0.03) and had no plans to offer supplemental screening compared to BDNL facilities (P < 0.02). CONCLUSION: Facilities in BDNL states often offer supplemental screening compared to facilities in non-BDNL states. Compared to BDNL facilities, a statistically significant proportion of non-BDNL facilities had no supplemental screening nor plans for implementation. Our data suggest that upcoming federal BDNL will impact how supplemental screening is addressed in currently non-BDNL states.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Factors associated with MRI detection of occult lesions in newly diagnosed breast cancers.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for newly diagnosed breast cancer remains controversial. We examined factors associated with detection of occult multicentric, multifocal, and contralateral malignant lesions only seen by MRI. METHODS: We performed a retrospective analysis of consecutive patients undergoing preoperative MRI for breast cancer. Clinicopathologic data were assessed regarding the findings of multifocality, multicentricity, and the presence of contralateral lesions. We analyzed the association of factors with these findings on MRI. RESULTS: Of 857 patients undergoing MRI, 770 patients met inclusion criteria. Mean age was 54.7 years. Biopsy-proven detection rates by MRI for multifocal, multicentric, and contralateral cancers were 6.2% (48 of 770), 1.9% (15 of 770) and 3.1% (24 of 770), respectively. African American race and heterogeneously or extremely dense mammographic density were associated with multifocal cancers on MRI. Larger lesion size and mammographic density were associated with multicentric cancers. Invasive lobular carcinoma (ILC) and progesterone receptor (PR)-positivity were associated with contralateral cancers. CONCLUSIONS: African American race, heterogeneously or extremely dense mammographic density, ILC, and PR-positivity were associated with additional biopsy-proven cancers based on MRI. These factors should be considered when assessing the clinical utility of preoperative breast MRI.

Clinical findings and outcomes of MRI staging of breast cancer in a diverse population.

BACKGROUND: The performance of magnetic resonance imaging (MRI), the effect of patient factors, and resulting surgical management in underserved and ethnically diverse breast cancer (BC) patient populations have been understudied. METHODS: We retrospectively analyzed the data of 1116 consecutive patients who were newly diagnosed with in situ or invasive BC with preoperative staging MRI. Non-index lesions (NILs) were defined as abnormal MRI findings with BI-RADS score of 4 or 5 in breast or axillary nodes not previously detected by conventional imaging. Occult cancers (OCs) were NILs found to be malignant by biopsy or surgery. Logistic regression was used to examine associations between probabilities of NILs or OCs and patient characteristics. RESULTS: Staging MRI detected NILs and OCs in 24% and 7.5% of patients, respectively. Of 1116 patients, 271 (24%) had 327 NILs, and 84 (7.5%) had 87 OCs. Follow-up information was available for 306 NILs. Ipsilateral breast NILs (n = 124) were seen in 115 patients (10.3%), with OCs (n = 51) seen in 48 patients (4.4%). Contralateral breast NILs (n = 134) were seen in 118 (10.6%) patients, with OCs (n = 20) seen in 20 patients (1.8%). Laterality (p < 0.001) and disease stage (p = 0.018) were associated with probability of OC. Patients without BRCA mutations had a significantly higher probability of having NILs (p = 0.003) but not OCs. CONCLUSIONS: Our study provides useful estimates of the rates of NILs and OCs anticipated in a younger, uninsured, ethnically diverse population. Prospective trials and larger pooled retrospective analyses are needed to define the long-term impacts of MRI staging after a BC diagnosis.

Are we overtreating intraductal papillomas?

BACKGROUND: The management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial regarding whether excision is required. We evaluated whether excision of IDPs might be overtreatment based on a consecutive patient population where all IDPs were routinely excised. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients treated with excision of IDPs at our institution from 2009 to 2016. We evaluated the rate of upgrade of IDPs on CNB and factors predicting for malignant upgrade. RESULTS: Of 153 CNB specimens, 136 (88.9%) were IDPs without atypia and 14 (9.2%) showed atypia. The overall upgrade rate on final pathology was 7.3% with 1.3% for invasive cancer, 2.7% for ductal carcinoma in situ, and 3.3% for atypical ductal hyperplasia. Of the 14 patients with atypia on CNB, two of these patients (14.2%) were found to have ductal carcinoma in situ. In the absence of atypia on CNB, upgrade rates were 1.5% for invasive and 1.5% for in situ carcinoma. Personal history of breast cancer and magnetic resonance imaging-guided biopsy predicted for malignant upgrade. CONCLUSIONS: IDPs on CNB have a low chance of harboring an occult malignancy. Given the low probability of upgrade to invasive breast cancer, it is reasonable to consider watchful surveillance in the absence of a prior personal history of breast cancer or atypia on CNB.

Accuracy of Contrast-Enhanced Ultrasound Compared With Magnetic Resonance Imaging in Assessing the Tumor Response After Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVES: This pilot study compared contrast enhanced ultrasound (US) with contrast-enhanced magnetic resonance imaging (MRI) in assessing the treatment response in patients with breast cancer receiving preoperative neoadjuvant chemotherapy (NAC). METHODS: This prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study included 30 patients, from January 2014 to October 2015, with invasive breast cancer detected by mammography, conventional US imaging, or both and scheduled for NAC. Informed consent was obtained. Contrast-enhanced US (perflutren lipid microspheres, 10 µL/kg) and MRI (gadopentetate dimeglumine, 0.1 mmol/kg) scans were performed at baseline before starting NAC and after completing NAC before surgery. Results of the imaging techniques were compared with each other and with histopathologic findings obtained at surgery using the Spearman correlation. Tumor size and enhancement parameters were compared for 15 patients with contrast-enhanced US, MRI, and surgical pathologic findings. RESULTS: The median tumor size at baseline was 3.1 cm on both contrast-enhanced US and MRI scans. The Spearman correlation showed strong agreement in tumor size at baseline between contrast-enhanced US and MRI (r = 0.88; P < .001) but less agreement in tumor size after NAC (r = 0.66; P = .004). Trends suggested that contrast-enhanced US (r = 0.75; P < .001) had a better correlation than MRI (r = 0.42; P = .095) with tumor size at surgery. Contrast-enhanced US was as effective as MRI in predicting a complete pathologic response (4 patients; 75.0% accuracy for both) and a non-complete pathologic response (11 patients; 72.7% accuracy for both). CONCLUSIONS: Contrast enhanced US is a valuable imaging modality for assessing the treatment response in patients receiving NAC and had a comparable correlation as MRI with breast cancer size at surgery.

Targeted Intraoperative Radiotherapy for the Management of Ductal Carcinoma In Situ of the Breast.

Multiple long-term studies have demonstrated a propensity for breast cancer recurrences to develop near the site of the original breast cancer. Recognition of this local recurrence pattern laid the foundation for the development of accelerated partial breast irradiation (APBI) approaches designed to limit the radiation treatment field to the site of the malignancy. However, there is a paucity of data regarding the efficacy of APBI in general, and intraoperative radiotherapy (IORT), in particular, for the management of ductal carcinoma in situ (DCIS). As a result, use of APBI, remains controversial. A prospective nonrandomized trial was designed to determine if patients with pure DCIS considered eligible for concurrent IORT based on preoperative mammography and contrast-enhanced magnetic resonance imaging (CE-MRI) could be successfully treated using IORT with minimal need for additional therapy due to inadequate surgical margins or excessive tumor size. Between November 2007 and June 2014, 35 women underwent bilateral digital mammography and bilateral breast CE-MRI prior to selection for IORT. Patients were deemed eligible for IORT if their lesion was ≤4 cm in maximal diameter on both digital mammography and CE-MRI, pure DCIS on minimally invasive breast biopsy or wide local excision, and considered resectable with clear surgical margins using breast-conserving surgery (BCS). Postoperatively, the DCIS lesion size determined by imaging was compared with lesion size and surgical margin status obtained from the surgical pathology specimen. Thirty-five patients completed IORT. Median patient age was 57 years (range 42-79 years) and median histologic lesion size was 15.6 mm (2-40 mm). No invasive cancer was identified. In more than half of the patients in our study (57.1%), MRI failed to detect a corresponding lesion. Nonetheless, 30 patients met criteria for negative margins (i.e., margins ≥2 mm) whereas five patients had positive margins (<2 mm). Two of the five patients with positive margins underwent mastectomy due to extensive imaging-occult DCIS. Three of the five patients with positive margins underwent successful re-excision at a subsequent operation prior to subsequent whole breast irradiation. A total of 14.3% (5/35) of patients required some form of additional therapy. At 36 months median follow-up (range of 2-83 months, average 42 months), only two patients experienced local recurrences of cancer (DCIS only), yielding a 5.7% local recurrence rate. No deaths or distant recurrences were observed. Imaging-occult DCIS is a challenge for IORT, as it is for all forms of breast-conserving therapy. Nonetheless, 91.4% of patients with DCIS were successfully managed with BCS and IORT alone, with relatively few patients requiring additional therapy.

Modified Bi-Rads Scoring of Breast Imaging Findings Improves Clinical Judgment.

In contrast with the reporting requirements currently mandated under the Federal Mammography Quality Standards Act (MQSA), we propose a modification of the Breast Imaging Reporting and Data System (Bi-Rads) in which a concluding assessment category is assigned, not to the examination as a whole, but to every potentially malignant abnormality observed. This modification improves communication between the radiologist and the attending clinician, thereby facilitating clinical judgment leading to appropriate management. In patients with breast cancer eligible for breast conserving therapy, application of this modification brings to attention the necessity for such patients to undergo pretreatment biopsies of all secondary, synchronous ipsilateral lesions scored Bi-Rads 3-5. All contralateral secondary lesions scored Bi-Rads 3-5 also require pretreatment biopsies. The application of this modification of the MSQA demonstrates the necessity to alter current recommendations ("short-interval follow-up") for secondary, synchronous Bi-Rads 3 ("probably benign") image-detected abnormalities prior to treatment of the index malignancy.

Double-Blind Randomized 12-Month Soy Intervention Had No Effects on Breast MRI Fibroglandular Tissue Density or Mammographic Density.

Soy supplementation by patients with breast cancer remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in patients with breast cancer. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated patients with breast cancer (n = 66) and high-risk women (n = 29). We obtained digital mammograms and breast MRI scans at baseline and after 12 months of daily soy (50 mg isoflavones per day; n = 46) or placebo (n = 49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram were measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 × MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 × FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P = 0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P = 0.48). Results were comparable in patients with breast cancer and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography.

Malignancy rates after surgical excision of discordant breast biopsies.

BACKGROUND: Vacuum-assisted core-needle biopsy (VAB) is increasingly used to perform breast biopsies instead of automated-gun core-needle biopsy (CNB). The significance of discordance between radiologic and pathologic findings has not been well established in the era of VAB predominance. This retrospective study was conducted to determine the rate of malignancy after surgical excisional biopsy (EXB) of these lesions at our two institutions. MATERIALS AND METHODS: We reviewed medical records from January 2008-June 2013 to identify female patients who underwent EXB for a Breast Imaging-Reporting and Data System (BI-RADS) 4 or 5 lesions found to be benign and discordant on CNB. Clinicopathologic data were gathered, and analysis was performed using descriptive statistics. RESULTS: A total of 8081 core biopsies were performed in the study timeframe. Six of 81 (7.4%) patients who had an EXB for a benign discordant breast lesion were found to have malignant pathology (two invasive, four in situ). Four of 63 (6.3%) lesions originally biopsied by VAB were upgraded, compared with 2 of 17 (11.8%) originally biopsied by CNB. There were no statistically significant differences in the rates of upgrade to malignancy when data were stratified by BI-RADS score or method of biopsy. CONCLUSIONS: The overall rate of malignancy after EXB of benign discordant lesions was 7.4%. Despite the widespread adoption of VAB, EXB is still warranted for clarification of discordant radiologic-pathologic findings.

Mammographic findings after intraoperative radiotherapy of the breast.

Intraoperative Radiotherapy (IORT) is a form of accelerated partial breast radiation that has been shown to be equivalent to conventional whole breast external beam radiotherapy (EBRT) in terms of local cancer control. However, questions have been raised about the potential of f IORT to produce breast parenchymal changes that could interfere with mammographic surveillance of cancer recurrence. The purpose of this study was to identify, quantify, and compare the mammographic findings of patients who received IORT and EBRT in a prospective, randomized controlled clinical trial of women with early stage invasive breast cancer undergoing breast conserving therapy between July 2005 and December 2009. Treatment groups were compared with regard to the 1, 2 and 4-year incidence of 6 post-operative mammographic findings: architectural distortion, skin thickening, skin retraction, calcifications, fat necrosis, and mass density. Blinded review of 90 sets of mammograms of 15 IORT and 16 EBRT patients demonstrated a higher incidence of fat necrosis among IORT recipients at years 1, 2, and 4. However, none of the subjects were judged to have suspicious mammogram findings and fat necrosis did not interfere with mammographic interpretation.