PD05-03: Impact of Quantitative Measurement of HER2, HER3, HER4, EGFR, ER and PTEN Protein Expression on Benefit to Adjuvant Trastuzumab in Early-Stage HER2+ Breast Cancer Patients in NCCTG N9831.

e12533 Background: Obesity is associated with breast cancer development and worse survival. Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer patients, CLS are present in 36-50% of patients and have been associated with anthropometric parameters. Here we focus on HER2+ breast cancer. The role of adiposity in HER2+ breast cancer is conflicting which may be attributed to the tumour heterogeneity. Adiposity has also been shown to affect the local immune environment of solid tumours. However, the prognostic significance of CLS in HER2+ breast cancer is still unknown. Methods: We investigated the prognostic significance of CLS in a cohort of 219 patients with primary HER2+ breast cancer who were diagnosed between 1982 to 2012 in Southampton General Hospital. This cohort includes 76 HER2+ trastuzumab naïve patients and 143 HER2+ patients treated with adjuvant trastuzumab. We stained FFPE tumour samples for the expression of CD68, CD16 and CD32B on CLS and correlated these to clinical outcomes. CLS were defined as CLS within distant adipose tissue, CLS within the adipose-tumour border (B-CLS) and intratumoural CLS. CLS were quantified manually in full face sections by two independent scorers and descriptive and Cox regression analysis was carried out. Results: A total of 201 tumours were suitable for CLS analyses. The median follow-up was 34.74 months (range, 0.43-299.08). In the trastuzumab naive cohort, B-CLS≤1 and B-CLS > 1 were present in 37 (52.11%) and 34 (47.89%), respectively. In the trastuzumab treated cohort, B-CLS≤1 were identified in 69 (53.08%) and B-CLS > 1 were found in 61 (46.92%) of the tumours. CLS were more commonly found in the adipose-tumour border (60.89%) rather than in the distant adipose tissue (36.14%) or intratumorally (14.36%). The presence of any CLS was significantly associated with BMI≥25 kg/m2 (p = 0.018). There was strong evidence of association between CD68+CD32B+ B-CLS and BMI≥25 kg/m2 (p = 0.007). Co-expression of CD16 and CD32B by B-CLS was more frequent in patients with BMI≥25 kg/m2 (p = 0.036). Survival analysis showed shorter time to metastatic disease in patients with CD68+ B-CLS > 1 (p = 0.011) in the trastuzumab treated cohort. Subgroup analysis revealed that in the BMI≥25 kg/m2 group, patients with CD68+ B-CLS > 1 had shorter time to metastatic disease compared to patients with B-CLS≤1 (p = 0.004). Multivariate cox regression showed that B-CLS > 1 is an independent prognostic factor for shorter time to metastatic disease in patients with primary HER2+ breast cancer that received adjuvant trastuzumab (HR 6.81, 95%CI (1.38-33.54), p = 0.018). Conclusions: B-CLS can be potentially used as a predictive biomarker to optimize the stratification and personalisation of treatment in HER2-overexpressed breast cancer patients.

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Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.523 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 523-523 ◽

Cited By ~ 21

Author(s):

M. Y. Halyard ◽

T. M. Pisansky ◽

L. J. Solin ◽

L. B. Marks ◽

L. J. Pierce ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Phase Iii ◽

Breast Cancer Patients ◽

Cardiac Events ◽

Concurrent Administration ◽

Adjuvant Trastuzumab ◽

Her2 Breast Cancer ◽

Significant Difference

523 Background: Adjuvant trastuzumab (Herceptin [H]) with chemotherapy improves outcome in HER2+ breast cancer (BC). Preclinical studies suggest H may enhance RT. We herein assess if H given with adjuvant RT increases adverse events (AE) after breast conserving surgery or mastectomy. Methods: N9831 randomized 3505 women with pT1–3N1–2M0, pT2–3N0M0, or pT1cN0M0 (ER/PR negative) HER2+ BC to doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T), AC→T→H, or AC→TH→H. Post-lumpectomy breast ± nodal RT was recommended, as was post-mastectomy chest wall + nodal RT (>3 nodes +); internal mammary RT was prohibited. RT started within 5 weeks of completion of T and allowed concurrently with H. 2324 eligible patients were enrolled on study prior to April 25, 2004: 1460 patients receiving RT are available for analysis of RT-associated AEs. Also, 1286 patients on +H arms who completed T (908 +RT and 378 -RT) are available for analysis of clinical cardiac events (CE). Rates of RT-associated AEs were compared across treatment arms, and rates of CE were compared for +RT vs -RT patients within +H arms. All reported p-values are for chi-squared statistics. Results: With a median follow-up of 1.5 years, significant differences among arms in RT-associated AEs were not identified. No significant differences across arms in +RT patients existed in the incidence of skin reaction (p=0.78), pneumonitis (p=0.78), dyspnea (p=0.87), cough (p=0.54), esophageal dysphagia (p=0.26), or neutropenia (p=0.16). There was a significant difference in +RT patients in the incidence of leukopenia (p=0.02) with higher incidence rates in the arms receiving H. RT did not increase the frequency of CE. In the AC→T→H arm, the incidence of CE was 2.2% in +RT patients versus 2.9% in -RT patients. In the AC→TH→H arm, the incidence of CE was 1.5% in +RT patients versus 6.3% in -RT patients. No difference in CE was seen between left- and right-sided RT fields in +RT patients in either +H arm. Conclusion: Concurrent administration of adjuvant RT with H in early stage breast cancer patients is not associated with an increased incidence of acute RT AEs. Further follow-up is required to assess late AEs. No significant financial relationships to disclose.

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Does preoperative MRI accurately stratify early-stage HER2 + breast cancer patients to upfront surgery vs neoadjuvant chemotherapy?

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06331-3 ◽

2021 ◽

Author(s):

Astrid Botty van den Bruele ◽

Emanuela Ferraro ◽

Varadan Sevilimedu ◽

Molly P. Hogan ◽

Sidra Javed-Tayyab ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Early Stage ◽

Breast Cancer Patients ◽

Her2 Breast Cancer

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Assessment of Survival and Cardiotoxicity of Adjuvant Trastuzumab among HER2 Breast Cancer Patients in an Oncology Centre in Malaysia

Journal of Clinical and Health Sciences ◽

10.24191/jchs.v3i1.6156 ◽

2018 ◽

Vol 3 (1) ◽

pp. 33

Author(s):

Harissa Husainy Hasbullah ◽

Anita Bustamam ◽

Tho Lye Munn ◽

Vincent Phua

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Disease Free Survival ◽

Metastatic Breast ◽

Left Ventricular ◽

Rank Test ◽

Breast Cancer Patients ◽

Adjuvant Trastuzumab ◽

Her2 Breast Cancer

Introduction: Adjuvant trastuzumab has been used in human epidermal growth factor-2 (HER2) breast cancer to improve survival but with concern of cardiotoxicity. Our study is the first to review efficacy and toxicity of adjuvant trastuzumab in Malaysia. Methods: This is a retrospective cohort study on HER2 non metastatic breast cancer patients in University Malaya Medical Centre diagnosed between October 2006 and May 2011. Two cohorts were created based on whether or not they received adjuvant trastuzumab. Disease free survival (DFS) and overall survival (OS) for both groups were estimated using Kaplan Meier method and compared using Log rank test. Cox proportional hazards regression models analysed for potential covariates of age, tumour size and grade, node and estrogen receptor (ER) status. Trastuzumab cardiotoxicity was defined as left ventricular systolic dysfunction or heart failure with or without symptoms and graded using Common Terminology Criteria for Adverse Events (CTCAE 4.0). Results: 170 HER2 non metastatic breast cancer patients were identified. Thirty-three received trastuzumab and 136 did not. Median age was 53.4 ± 10.3 years old. Significantly more ER negative patients received trastuzumab. Four years DFS in ‘trastuzumab’ versus ‘no trastuzumab’ cohort was 90.9% vs 74.5% (p = 0.027). Four years OS was 91% vs 84.7% (p = 0.30) respectively. Majority tolerated trastuzumab with no toxicity. Five patients (15.2%) experienced cardiotoxicity (all grade I).Conclusions: Adjuvant trastuzumab significantly improved DFS in HER2 breast cancer. Treatment was well tolerated. With this we propose the justification for adjuvant trastuzumab in HER2 breast cancer in our population.

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Abstract P4-09-08: PTEN Protein Expression in Postmenopausal Steroid Receptor Positive Early Breast Cancer Patients Treated with Adjuvant Tamoxifen

10.1158/0008-5472.sabcs10-p4-09-08 ◽

2010 ◽

Cited By ~ 1

Author(s):

ZM Milovanovic ◽

SV Susnjar ◽

VS Plesinac-Karapandzic ◽

ZD Juranic ◽

SB Tatic ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Early Breast Cancer ◽

Steroid Receptor ◽

Adjuvant Tamoxifen ◽

Breast Cancer Patients ◽

Pten Protein

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Adjuvant treatment of early-stage HER2+ elderly breast cancer patients: A retrospective, multicenter French study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.636 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 636-636

Author(s):

Philippe Barthelemy ◽

Karine Bassot ◽

Florence Joly ◽

Isabelle Ray Coquard ◽

Gilles Freyer ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Early Stage ◽

Single Agent ◽

Her2 Status ◽

Routine Practice ◽

Breast Cancer Patients ◽

Her2 Breast Cancer

636 Background: Trastuzumab (T) is the standard of care for the adjuvant treatment of early stage, HER2+ breast cancer (BC). However, few data are available for elderly HER2+ breast cancer patients in this setting. In this current study, the patterns of care for elderly HER2+ early stage BC in 7 French cancer centres was evaluated. Methods: Medical records of all consecutive early stage HER2+ BC patients over 70 years old treated between 2006 and 2011 among participating centres were retrospectively reviewed. Specific factors such as age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics, follow-up and cardiotoxicity data were analysed. Results: One hundred and two patients were identified, median age 75.4 (range 70-95). Elderly patients presented mostly (57%) large tumors (pT ≥2), and positive lymph node involvement (n=61). Trastuzumab-based adjuvant treatment was administered in 62% of patients (n=63). 54% of patients (n=55) received adjuvant chemotherapy whereas five patients received neoadjuvant chemotherapy. Chemotherapy without T was administered in 2 additional patients. Anthracyclines (A)-Taxanes (Ta) combination-based chemotherapy was given in 27% of patients (n=16), whereas 38% received a Ta-based chemotherapy (n=23), 35% (n=19) an A-based chemotherapy. Five patients received single-agent T. Treatment delays for T were required in 37% of patients (n=23) among whom 15 and 8 permanently or temporarily stopped T, respectively. The most frequent reason for interrupting or delaying therapy was cardiotoxicity (n=12) as well as patients refusal (n=7). A ≥ 10% decrease in LVEF was observed in 18/63 (29%) of patients, among whom T was stopped in 12. After a median 33 months follow-up, the median progression-free survival was not reached in patients receiving T-based therapy. The 2 and 3-year PFS rate were 94 and 89.5%, respectively. Conclusions: In routine practice only 62% of elderly early stage HER2+ BC patients are treated with a neoadjuvant or adjuvant T-based regimen. However, less than 50% of all patients completed their therapy. A-based chemotherapy was administered in around 60% of treated patients, and could explain cardiotoxicity in this setting.

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