Judith Hirshfield-Bartek

Abstract P4-02-08: MRI changes in breast skin following preoperative therapy for inflammatory breast cancer (IBC)

Purpose: Standard treatment for IBC includes preoperative systemic therapy (PST), followed by mastectomy (M) and adjuvant radiation (R). Determining the optimal sequencing of M and R after PST may be difficult when clinical changes suggest residual disease within breast skin. With the goal of selecting appropriate patients (pts) for M prior to R, we correlated pathologic disease response in breast skin with changes in skin thickness and enhancement determined by MRI. Methods: An IRB approved database of IBC pts evaluated at Dana Farber Cancer Institute (DFCI) from 1997-2013 was used for retrospective analysis. 40 pts met criteria: confirmed diagnosis of IBC, completed PST followed by M without preoperative R. Baseline and post-PST breast MRI imaging was reviewed. Using the ACR BI-RADS lexicon, we recorded skin thickness, qualitative enhancement and kinetic analysis using computer-aided detection post-processing software. Findings were correlated with pathologic response in skin found at M. Results: MRI showed baseline skin thickening in all 40 pts (median 6mm, range 3-13mm). Although 34 (85%) had persistent skin thickening post-PST (median 4 mm, range MRI showed qualitative skin enhancement at baseline in 39/40 pts. 29 (73%) had medium/fast initial phase kinetics: 25 persistent delayed phase kinetics, 2 wash-out, 2 plateau. 20 pts had residual qualitative skin enhancement post-PST; 11 pts (28%) had medium/fast initial phase kinetics, all persistent delayed kinetics. The decrease in skin thickness was significantly greater among the 19 pts achieving resolution of skin enhancement post-PST compared with the decrease in skin thickness among the 20 pts with residual skin enhancement (p=0.02). 8 pts (20%) had residual tumor within the skin at M. All 8 pts had thicker skin on post-PST MRI (median 5 mm, range 3-13mm) compared with pts without residual disease in the skin (median 3.5mm, range Conclusion: Although IBC pts have skin thickening demonstrated by MRI at baseline, there is a statistically significant reduction in the skin thickness following successful PST. This correlates with a reduction in enhancement of the skin shown by MRI imaging. More substantial and persistent skin thickening with enhancement was seen in the setting of residual dermal lymphatic involvement following the completion of PST, though this study is too small to detect any significant correlation. Since an accurate assessment of residual disease in breast skin is vital in determining the optimal sequencing of M and R following PST in IBC pts, MRI evaluation of skin thickness and enhancement may be a useful tool to predict residual disease and guide surgical management of IBC. Citation Format: Yeh E, Rives A, Guo H, Regan M, Birdwell R, Nakhlis F, Bellon J, Warren L, Hirshfield-Bartek J, Jacene H, Dominici L, Overmoyer B. MRI changes in breast skin following preoperative therapy for inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-08.

Abstract P1-12-08: Factors associated with delays in chemotherapy initiation among patients with breast cancer

Background: National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI designated comprehensive cancer center. Methods: We identified 523 patients who received post-operative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target timeframe, and unacceptable delay in chemotherapy initiation (UCD) as more than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype testing in HR+ patients. Results: Median days between LDS and chemotherapy initiation was 34 (IQR 15), with 30% of patients starting within 28 days of LDS and 23% having UCD (Table 1). Tumor characteristics such as subtype and stage affected UCD; patients with HR+ or HER2+ tumors were more likely to be delayed compared to those with TNBC. Patients with stage I disease were more likely to be delayed as well as patients undergoing mastectomy or mastectomy with reconstruction. Patients whose pathology sign-out was more than 10 days post-operatively were more likely to be delayed. A higher proportion of UCD was found in HR+ patients (31%) who received an Oncotype recurrence score compared to those who did not (20%). Conclusions: This study provides insight into populations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care. Citation Format: Losk K, Vaz Duarte Luis I, Camuso K, Lloyd M, Kadish S, Hirshfield-Bartek J, Cutone L, Golshan M, Lin N, Bunnell C. Factors associated with delays in chemotherapy initiation among patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-08.

Abstract P6-18-02: Patterns of breast reconstruction in patients diagnosed with inflammatory breast cancer

Background Inflammatory Breast Cancer (IBC) is a rare and aggressive type of breast cancer treated by multimodality therapy. Due to the presence of dermal lymphatic involvement by disease it is unknown whether a skin sparing mastectomy (SSM) would be safe, even after completion of preoperative chemotherapy, therefore immediate breast reconstruction (BR) following modified radical (MRM) is discouraged. We sought to explore the patterns of BR outcomes in IBC patients (pts) and to evaluate their surgical outcomes. Methods A retrospective analysis was performed using an IRB-approved database of IBC pts evaluated at Dana Farber Cancer Institute (DFCI) from 1997 until 2014. Pts with stage III IBC who received preoperative systemic therapy followed by MRM and post-mastectomy radiation (PMRT) were analyzed. Receipt and timing of BR, post-operative morbidity and subsequent esthetic issues were collected. We also analyzed oncologic events which may have hindered receipt of BR. Results 318 pts were enrolled in the IBC registry at DFCI between 1997 and 2014. 181 pts with stage III IBC were identified, with a median follow-up of 57 months (mo) from MRM. 33/181 pts (18%) underwent BR; 2 pts were not evaluable due to lack of details concerning BR. 12 pts had immediate BR, 10 of which were performed elsewhere, prior to initial evaluation at DFCI. These included 3 tissue expander (TE) reconstructions, 3 single stage implants, 1 deep inferior epigastric perforator (DIEP) flap, 4 transverse rectus abdominis myocutaneous (TRAM) flaps, 1 latissimus dorsi (LD) flap. 19 had delayed BR. These included 1 TE, 5 DIEP flaps, 2 LD flap, 1 TE+LD flap, 10 TRAM flaps. Delayed BR occurred at a median of 13 mo (range 3-64 mo) following completion of PMRT. Complications post-BR were rare. Among the immediate BR pts, 1 pt with a TRAM flap BR required a reoperation 15 days (d) following BR for a partial TRAM flap necrosis. Among the delayed BR pts, one had a reoperation for abdominal TRAM flap donor site wound dehiscence 29 d after BR. Another delayed BR pt, who had a TE+LD flap BR, had her reconstruction implant removed due to chronic hematoma 79 mo after her initial BR; this occurred following 3 operative attempts to salvage her reconstruction by evacuating the hematoma. Overall, 12 reoperations were performed including 6 immediate BR (6/19 (31.6%) and 6 delayed BR pts (6/12 (50.0%); 6 of these reoperations (50%) were done for minor esthetic issues, such as reconstruction revisions for fat necrosis and capsular contracture, in addition to the more significant surgeries described above. Among 148 pts who did not undergo BR, 69 (47%) had disease recurrence following MRM (66 distant +/- local-regional recurrence (LRR); 3 LRR only); within 12 mo of MRM disease recurrence developed in 22% of pts (33/148). Conclusion Only 11% of pts presenting with stage III IBC recieved delayed BR in this retrospective analysis of 181 pts. The majority of these pts achieved successful BR, except for 1 pt. It is possible that BR was not sought more frequently due to a fairly high rate of distant disease relapse (47% in this cohort). Further studies addressing the outcomes of BR in IBC pts are needed in order to assist in counseling pts regarding their reconstructive expectations. Citation Format: Nakhlis F, Regan M, Chun YS, Dominici LS, Jacene HA, Yeh ED, Bellon JR, Warren LE, Hirko K, Hirshfield-Bartek J, Hazra A, Overmoyer BA. Patterns of breast reconstruction in patients diagnosed with inflammatory breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-18-02.

Abstract P6-14-08: Risk factors for developing inflammatory breast cancer: Unique trends among a single patient population

Introduction: Inflammatory breast cancer (IBC) is a virulent form of breast cancer, characterized by skin erythema and edema associated with enlargement of the breast rapidly occurring within 3-6 months (mo). Because of its rarity ( Methods: This study utilized retrospective data obtained from an IRB approved database of 275 patients (pts) with IBC evaluated at Dana Farber Cancer Institute (DFCI) from 1997-2012. Pts with confirmed invasive breast cancer had documented clinical characteristics of IBC clinically staged as T4d. The statistical software JMP 10 was used to perform statistical tests. Chi Square Tests, Fisher’s Exact Tests, and descriptive statistics were compiled. Results: The mean age of diagnosis among our study population was 50.2 years (yrs). IBC pts were more frequently diagnosed when premenopausal (55%) versus (v) postmenopausal (45%); 25% of pts had metastases upon presentation. The majority of patients (77%) were overweight (BMI 25-29.9) or obese (BMI≥30). More premenopausal pts (80.3%) had a BMI >25 v postmenopausal pts (73.5%). We observed no association with BRCA status among those undergoing genetic testing (13% BRCA positive (pos); 54 tested); however 52% of pts had a family history of breast cancer (5% BRCA pos). The majority of pts (81%) did not undergo genetic testing. The most common IBC subtype was HER2 pos (40%); 19% were triple negative (neg), and 16% were hormone receptor (HR) pos/HER2 neg. We also observed a trend of a longer duration of symptoms prior to diagnosis among younger pts. The mean age of pts who experienced >6 months (mo) of symptoms prior to diagnosis was 42 yrs v the mean age of 51 yrs among those experiencing Conclusion: This retrospective epidemiologic analysis demonstrated various trends in a single population of IBC pts. The association of high BMI and risk of developing IBC among premenopausal women contrasts with that seen in the non-IBC group, i.e. high BMI is a risk factor for non-IBC only among postmenopausal women. Targeting the obesity crisis may be a means of reducing the risk of developing IBC among younger women. A differentiating feature of IBC is the rapid onset of signs and symptoms of IBC, and yet, younger pts had a significant delay in diagnosis of >6 mo compared with older pts. This emphasizes the urgency to educate both pts and providers about IBC and facilitate rapid diagnostic procedures. The seasonal relationship with diagnosis observed in this cohort of IBC pts is intriguing. Investigators have hypothesized an infectious etiology contributing to the development of IBC, namely infection by viruses or bacterial pathogens may play a role in the pathophysiology of IBC. These unique trends seen in the DFCI IBC population deserve further investigation. Citation Format: Randie E White, Laura E Warren, Jennifer R Bellon, Faina Nakhlis, Heather A Jacene, Eren D Yeh, Judith Hirshfield-Bartek, Beth Overmoyer, Inflammatory Breast Cancer International Consortium. Risk factors for developing inflammatory breast cancer: Unique trends among a single patient population [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 P6-14-08.

Abstract P6-14-09: Clinical outcomes of triple negative inflammatory breast cancer treated with contemporary anthracycline and taxane preoperative therapy support further investigation of therapeutic targets

Background: Approximately 40-50% of inflammatory breast cancer (IBC) is triple negative (TN), defined as estrogen and progesterone receptor and HER2 negative. The poor prognosis associated with TN- IBC lends itself to active investigation of novel therapies to improve outcome. Dr. Kornelia Polyak’s laboratory has demonstrated a significant association of JAK2/STAT3 pathway activity in TN-IBC (Overmoyer, Cancer Res 2012). In preparation of designing a clinical trial investigating the effect of JAK2 inhibition by ruxolitinib on biologic parameters and subsequent use in neoadjuvant chemotherapy (NAC) for TN-IBC, we determined historical outcomes resulting from a single institution’s contemporary standard treatment of TN-IBC. Methods: Among the 273 pts enrolled in the IRB approved IBC database at the Dana Farber Cancer Institute, 28 pts were identified with Stage III (T4d,NX,M0)TN-IBC diagnosed from 1/1/1999 to 12/31/2011 who were treated with standard NAC including anthracycline, cyclophosphamide and taxane. Time to treatment failure (TTF) was defined from diagnosis (dx) to first progression or recurrence; time to distant metastasis (TDM) was defined from dx to first metastasis at a distant site; overall survival was defined from dx to death from any cause. Subsequent to NAC, 25 pts underwent modified radical mastectomy (MRM) and radiation. For those 25 pts, disease-free survival (DFS) was defined from MRM to first recurrence or death; time to local/regional recurrence (LRR) was defined from MRM with death as competing risk. All time-to event endpoints were censored at the date last known alive if an event was not observed. Results: Among 28 patients, the median TTF was 19 months (mo) with 67% free from progression/recurrence at 1 year (yr) after dx (95% CI, 51-87%). Median TDM was 20 mo with 78% free from distant metastases at 1 yr (CI 64-95%). Most patients (13/21) had multiple sites of first distant metastasis including: lung (7), contralateral axilla (7), bone (6), liver (3) and CNS (3). Median OS was 34 mo since dx (Table). Among 25 patients who underwent MRM, median DFS was 15 mo with 1-yr DFS of 58% (42-82%); the cumulative probability of LRR was 13% and 33% at 1 and 2 yr. Conclusions: This retrospective analysis of clinical outcomes of Stage III TN-IBC treated with contemporary anthracycline/taxane regimes is consistent with previously reported outcomes using historical NAC regimens. (Li, et al, the Oncologist 2012). These dismal rates of 49% 3-year OS from diagnosis and 58% 1-yr DFS following MRM demand more active investigation into novel targeting agents which can be combined with standard NAC specifically for the treatment of TN-IBC; a disease that has no known therapeutic target. For this reason DFCI is actively investigating the role of inhibiting the JAK2/STAT3 pathway using ruxolitinib in conjunction with standard weekly paclitaxel followed by AC as NAC for TN-IBC. Clinical trial information: NCT01796197. Citation Format: Beth Overmoyer, Hao Guo, Laura E Warren, Jennifer R Bellon, Kornelia Polyak, Faina Nakhlis, Judith Hirshfield-Bartek, Heather Jacene, Eren D Yeh, Meredith Regan, Inflammatory Breast Cancer International Consortium. Clinical outcomes of triple negative inflammatory breast cancer treated with contemporary anthracycline and taxane preoperative therapy support further investigation of therapeutic targets [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 P6-14-09.

Standardizing coordination between surgical oncology and reconstructive surgery for breast cancer patients undergoing mastectomy with immediate reconstruction.

110 Background: Timely diagnosis and treatment of breast cancer, endorsed by organizations such as ASCO and NCCN, are essential to ensure optimal clinical outcomes and patient satisfaction. Inefficient care coordination may adversely affect care quality. At our cancer center, 75% of patients who undergo mastectomy seek a reconstructive surgery consult and over 60% elect mastectomy with immediate reconstruction. We sought to evaluate and reduce the time to reconstructive surgery consult and first definitive surgery (FDS) by streamlining coordination between services. METHODS We studied 330 patients who underwent mastectomy with immediate reconstruction between January 2011 and April 2013. Time intervals between initial surgical consult, reconstruction consult, and FDS were calculated. After examining existing best practices in patient referral and scheduling, we established targets of 7 days from initial consult to reconstruction consult and 28 days from initial consult to FDS. To achieve these targets, facilitated sessions were held with administrative and clinical experts to create a standard referral and scheduling process, including a referral template and establishing surgical teams based on clinic and operating room alignment. The interventions were implemented over a 6-month period. RESULTS Mean days from initial consult to reconstructive surgery consult decreased, with significant improvement in reaching the 7 day target. No significant changes from time of initial consult to FDS were observed. CONCLUSIONS Standardizing coordination has led to timelier reconstructive surgery consults for patients undergoing mastectomy with immediate reconstruction. Other factors, such as operating room availability, pre-operative testing and patient preference should be explored to reduce the time to FDS. [Table: see text].

Abstract P3-10-06: Patterns of failure in patients with inflammatory breast cancer: the case for aggressive local/regional treatment

Background: While the survival of patients with inflammatory breast cancer (IBC) is dictated by the status of their distant metastases, local/regional control remains an important component of quality of life. We have sought to determine patterns of local/regional recurrence (LRR) in patients presenting with inflammatory breast cancer. Methods: The medical records of 92 patients (pts) diagnosed with IBC from 1997 until 2007 were reviewed. Pt cohorts were stratified by disease burden at presentation (metastatic or local/regional) and their tumor, treatment, and disease course were analyzed. Primary outcomes were time from diagnosis to LRR, time to distant recurrence, and overall survival (OS). Median follow-up (MFU) for the entire cohort was 6 years (yrs) (range 0.1 to 12.7 yrs); for those patients who presented with metastatic disease versus only local/regional disease, MFU is 2 yrs and 6 yrs, respectively. This study was approved by the hospital institutional review board. Results: Median age at diagnosis was 49 yrs (range 24 to 72). 68 (74%) patients were without evidence of metastatic disease on presentation. With 6yr MFU, 40/68 (59%) had disease recurrence at either local or distant sites, and 15/68 (22%) had documented LRR, either as the first or subsequent site of recurrence. Estimated 5yr OS is 64%. 24 (26%) pts presented with metastatic disease (lung, liver, distant lymph nodes, pleura). All of the 24 pts presenting with metastatic disease developed systemic disease progression; 12/24 (50%) also developed LRR, and for 9/12 pts the LRR was first progression or concurrent with distant progression. Eleven of the 24 pts did not receive radiation or surgery; and within this cohort, 7 (64%) pts developed LLR at a median time of 9 months after diagnosis. Six pts received radiation therapy without surgery; 3/6 (50%) developed LRR. One pt had surgery alone; this patient was not known to have LRR, although had limited follow-up. Six pts received radiation therapy and surgery; 1 for palliation and 5 to prevent LRR. Of these 5 pts, 1/5 (20%) developed LRR that extended to the contralateral breast at 1.2y after diagnosis. Among the 24 patients, the cumulative incidence of LRR was 29%, 37%, and 43% at 1yr, 2yr, and 3yr (accounting for competing risk of death). The median OS was 2.9 yrs and estimated 5yr OS was 36%. Conclusions: Pts with inflammatory breast carcinoma presenting with metastatic disease are at high risk for local/regional disease progression. Aggressive local therapy should be considered to prevent symptoms of uncontrolled local disease, despite an uncertain impact upon OS. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-06.

Abstract P5-02-01: Discrepancy between CT and FDG-PET/CT in the staging of patients with inflammatory breast cancer: Implications for radiation therapy treatment planning

Background: To compare suspected areas of cancer involvement based on the findings of CT and FDG-PET/CT in patients with inflammatory breast cancer (IBC) and to determine if discrepancies would modify radiation therapy treatment fields. Methods: This is a retrospective study of 29 consecutive female patients with IBC (median age 49 years, range 28–78) who had both CT and PET/CT scans prior to the initiation of systemic therapy. CT and PET/CT scans were obtained within a median of 3 days (range 0–64). CT and PET/CT scans were independently reviewed by a board-certified radiologist (PD) and a board-certified nuclear medicine physician (HJ), respectively. Findings were recorded by anatomic site and graded as negative, equivocal or positive for malignancy. Radiation fields were then determined by a breast radiation oncologist (JB) after separately reviewing the CT and PET/CT images. Discrepancies between the two modalities were recorded. The study was approved by the hospital institutional review board. Results: Seven of 29 patients (24%) had discrepant findings that likely would have resulted in a modification of radiation treatment fields and/or radiation dose. In four patients, internal mammary nodal involvement was suspected on PET/CT but not on CT. In two of these four patients, PET/CT also detected additional disease (supraclavicular in one patient and chest wall in the other) that likely would have required a change in radiation field and/or dose. Another patient had subpectoral adenopathy on PET/CT that was not considered abnormal on CT. One patient had equivocal findings in the infraclavicular region on CT which was negative on PET/CT. In one patient, body habitus limited the CT evaluation; more extensive infiltrative soft tissue and nodal disease was seen on PET/CT. In four patients, there were discrepant findings for distant disease that likely would have resulted in a change in management or additional imaging studies. In two of these cases, PET/CT showed a clearly positive finding that was negative or equivocal on CT. In an additional two cases, equivocal PET/CT findings would have resulted in additional testing that would not have been recommended by CT alone. In another 4 cases, metastatic disease was suspected based on CT, but additional sites (all in bone and not seen on CT) were suspected on PET/CT. Conclusions: Inflammatory breast cancer patients have a high probability of presenting with extensive local/regional disease and distant metastases. In our IBC population, PET/CT imaging would have likely resulted in a change of radiation field or dose in 7 of 29 (24%) patients. Additionally, in four instances PET/CT suspected additional metastatic disease (14%). These discrepancies most commonly involved inclusion of an internal mammary nodal radiation field and identification of distant metastases. Pathologic verification of abnormal findings is necessary to verify these results. PET/CT imaging should be considered a standard component of radiographic staging for patients with IBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-02-01.