Pathologic Complete Response (pCR) and Survival of Women with Inflammatory Breast Cancer (IBC): An Analysis Based on Biologic Subtypes and Demographic Characteristics

In this US-based study of the National Cancer Database (NCDB), we examined 8550 patients diagnosed with non-metastatic, invasive inflammatory breast cancer (IBC) who received surgery from 2004–2013. Patients were grouped into four biologic subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2−). On average, women were 56 years of age at diagnosis and were followed for a median of 3.7 years. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5 cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p < 0.0001). Patients experiencing pathologic complete response (pCR, 12%) vs. non-pCR had superior 5-year overall survival (OS) (77% vs. 54%) (p < 0.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p < 0.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p < 0.0001). In this analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.

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Pathologic Complete Response (pCR) and Survival of Women with Inflammatory Breast Cancer (IBC): An Analysis Based on Biologic Subtypes and Demographic Characteristics

10.20944/preprints201810.0383.v1 ◽

2018 ◽

Author(s):

Tithi Biswas ◽

Charulata Jindal ◽

Timothy Fitzgerald ◽

Jimmy Efird

Keyword(s):

Breast Cancer ◽

Inflammatory Breast Cancer ◽

Private Health Insurance ◽

Triple Negative ◽

Pathologic Complete Response ◽

Multivariable Analysis ◽

Complete Response ◽

National Cancer Database ◽

Tumor Patient ◽

Poorly Differentiated

The aim of this study was to examine pathologic complete response (pCR) and overall survival (OS) of patients diagnosed with non-metastatic inflammatory breast cancer (IBC). A total of N=8,550 cases undergoing surgery were identified between 2004-2013, using the National Cancer Database (NCDB). Patients were grouped into 4 biologic subtypes (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). The median age at diagnosis was 56 years. On average, women were followed for 3.7 years [interquartile range=3.0]. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p<.0001). Compared with non-pCR (54%), patients experiencing pCR had superior 5-year survival (77%) (p<.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p<.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p<.0001). In this large multicentric analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.

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Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e11550 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e11550-e11550

Author(s):

Stephen Tiley ◽

Rachel Elizabeth Raab ◽

Lisa Sheri Bellin ◽

Jan H. Wong ◽

Jackie Unger ◽

...

Keyword(s):

Breast Cancer ◽

Inflammatory Breast Cancer ◽

Triple Negative ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Metronomic Chemotherapy ◽

Complete Response ◽

Weekly Paclitaxel ◽

Breast Cancers ◽

Grade 3

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.

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Pathologic complete response rates observed in women with locally advanced and inflammatory breast cancer receiving neoadjuvant carboplatin and paclitaxel.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1035 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1035-1035 ◽

Cited By ~ 1

Author(s):

Arvind Manohar Shinde ◽

John H Yim ◽

Laura Kruper ◽

Courtney Vito ◽

Steven L. Chen ◽

...

Keyword(s):

Breast Cancer ◽

Inflammatory Breast Cancer ◽

Triple Negative ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Hematologic Malignancies ◽

Cancer Center ◽

Dose Reductions

1035 Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NCT) is predictive of outcome in patients with locally advanced breast cancer (LABC). A non-anthracycline containing NCT regimen (Sikov et al. JCO 10/09) may reduce the risk of associated secondary hematologic malignancies and cardiac toxicity while yielding comparable pCR rates. Methods: A retrospective review of all LABC and inflammatory breast cancer (IBC) cases treated from 4/09 to 12/11 with a NCT regimen of carboplatin (AUC of 6, administered on day 1) and paclitaxel 80 mg/m2 (given weekly on a 21-28 day cycle) was conducted at the City of Hope Cancer Center (COHCC). Pts with HER2+ (HER+) tumors received trastuzumab during the NCT treatment. All pCRs (pCR of primary only – "pCR1°"; pCR of primary and lymph nodes – "pCR-All") were determined by a COHCC pathologist based on final surgical specimens. Results: 38 pts were identified, with 39 breast primaries; 18% had IBC, 62% of LABCs/IBCs were hormone receptor positive (HR+), 46% of tumors were HER2+, and 26% were triple negative. Median age was 51 [27-63]. All pts completed the planned number of cycles. Four pts required carboplatin dose reductions, 4 pts required dose reductions in paclitaxel, 3 pts had paclitaxel changed to nab-paclitaxel, and 17 pts required G-CSF to complete their planned treatment. One pt receiving trastuzumab experienced asymptomatic LVEF decline below normal limits. Conclusions: A non-anthracycline-containing NCT regimen of carboplatin/paclitaxel was well tolerated and resulted in high pCRs when given to triple negative (HER2-/HR-) pts, and HER2+ pts, especially with HER2+HR- subtypes. The findings warrant further studies of this regimen in a prospective randomized setting. [Table: see text]

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Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7103 ◽

2019 ◽

Vol 17 (4) ◽

pp. 348-356 ◽

Cited By ~ 2

Author(s):

Prashant Gabani ◽

Emily Merfeld ◽

Amar J. Srivastava ◽

Ashley A. Weiner ◽

Laura L. Ochoa ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Locoregional Recurrence ◽

Triple Negative ◽

Pathologic Complete Response ◽

Multivariable Analysis ◽

Complete Response ◽

Hazard Ratio ◽

Increased Risk

Background:This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR).Methods:This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors.Results:A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64–9.38;P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35–8.15;P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001).Conclusions:In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

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