Effect of Delay in Initiation of Adjuvant Trastuzumab and Dose Interruptions on Overall Treatment Outcome in Breast Cancer Patients, a Retrospective Study

Abstract Background HER2 amplification or protein over-expression is found in 20% of invasive breast cancers. It’s clearly associated with accelerated cell growth and proliferation and poor clinical outcome. The amplification of HER2 was historically an adverse prognostic factor associated with a higher risk of recurrence, lack of or lower levels of ER expression, and relative resistance to endocrine therapy and CMF based chemotherapy. Objectives We aimed in this study to assess the impact of delaying the initiation of adjuvant Trastuzumab for more than three months after the diagnosis of breast cancer and the effect of irregular and interrupted doses of adjuvant Trastuzumab, on progression free Survival, relapse, and overall survival (OS) among patients with breast cancer. Patients and Methods A Retrospective cohort study was conducted in Ain Shams University Hospitals. The study included one hundred patients with HER2 positive breast cancer. from January 2011 till December 2016 at the" Department of Clinical Oncology and Nuclear Medicine, Ain Shams University Hospitals". Results The median time to progression in group I was 19 months compared to 30 months in group II. There was statistically significant decrease median of group I compared to group II according to PFS. Conclusion We concluded that delays in the initiation of adjuvant treatment may be particularly harmful in patients with more aggressive tumor types.

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The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11576 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11576-e11576

Author(s):

Anastasios L. Boutis ◽

Sofia Chatzileontiadou ◽

Nikolaos Diamantopoulos ◽

Athanasios Pouptsis ◽

Chariklia Fotiou

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Ductal Carcinoma ◽

Advanced Breast ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Metastatic Setting ◽

Increased Risk

e11576 Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.

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Rate of reclassification of HER2-equivocal breast cancer cases to HER2-negative per the 2018 ASCO/CAP guidelines and response of HER2-equivocal cases to anti-HER2 therapy

PLoS ONE ◽

10.1371/journal.pone.0241775 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241775

Author(s):

James Crespo ◽

Hongxia Sun ◽

Jimin Wu ◽

Qing-Qing Ding ◽

Guilin Tang ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Disease ◽

Cancer Center ◽

Her2 Status ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Testing ◽

Primary Disease ◽

The Impact

Purpose The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer permits reclassification of cases with HER2-equivocal results by FISH. The impact of such reclassification is unclear. We sought to determine the proportion of HER2-equivocal cases that are reclassified as HER2-negative and the impact of anti-HER2 therapy on survival in HER2-equivocal cases. Methods We reviewed medical records of breast cancer patients who had HER2 testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline. The population was divided into 2 cohorts according to whether the biopsy specimen analyzed came from primary or from recurrent or metastatic disease. HER2 status was reclassified according to the 2018 ASCO/CAP guideline. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and the relationship between anti-HER2 therapy and clinical outcomes was assessed. Results We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease. Per the 2018 ASCO/CAP guideline, these cases were classified as follows: overall, HER2-negative 112 cases (80%), HER2-positive 1 (1%), and unknown 26 (19%); primary cohort, HER2-negative 85 (94%), HER2-positive 1 (1%), unknown 4 (4%); and recurrent/metastatic, HER2-negative 27 (55%) and unknown 22 (45%). Five patients in the primary-disease cohort and 1 patient in the recurrent/metastatic-disease cohort received anti-HER2 therapy. There was no significant association between anti-HER2 therapy and OS or EFS in either cohort (primary disease: OS, p = 0.67; EFS, p = 0.49; recurrent/metastatic-disease, OS, p = 0.61; EFS, p = 0.78. Conclusions The majority of HER2-equivocal breast cancer cases were reclassified as HER2-negative per the 2018 ASCO/CAP guideline. No association between anti-HER2 therapy and OS or EFS was observed. HER2-equivocal cases seem to have clinical behavior similar to that of HER2-negative breast cancers.

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registHER: Patient characteristics, treatment patterns, and preliminary outcomes in patients with HER2-positive (HER2+), hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21007 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21007-21007 ◽

Cited By ~ 1

Author(s):

D. A. Yardley ◽

P. A. Kaufman ◽

M. Mayer ◽

M. Ulcickas Yood ◽

E. Tan-Chiu ◽

...

Keyword(s):

Breast Cancer ◽

Randomized Clinical Trials ◽

Metastatic Breast ◽

Progression Free Survival ◽

Treatment Patterns ◽

Breast Cancers ◽

Breast Cancer Patients ◽

First Line ◽

Her2 Positive ◽

Small Patient Population

21007 Background: Approximately 50% of HER2+ breast cancers are HR+, however, the interaction between HER2 and HR is not completely understood. Patients with HR+/HER2+ or HR-/HER2+ tumors treated with trastuzumab + chemotherapy (CT) achieve similar clinical benefit. Retrospective analyses suggest that HER2+ tumors are resistant to hormone therapy (HT), particularly anti-estrogens, possibly due to estrogen receptor /HER2 interactions and quantitatively lower HR expression in HER2+/HR+ tumors. Conducting randomized clinical trials in HER2+/HR+ MBC is challenging given the small patient population. Methods: registHER is a prospective observational study of approximately 1000 patients with newly diagnosed (<6 months) HER2+ MBC treated in community or academic settings. Baseline characteristics and treatment patterns in patients with HR+ vs HR-, HER2+ MBC receiving first-line therapy were studied in this analysis. The influence of adjuvant HT on disease-free intervals (DFI) from time of diagnosis and MBC treatment selection in patients with HR+/HER2+ tumors was examined. Results: Of 976 patients with HER2+ MBC and recorded tumor HR status, those with HR+ MBC (54.9%) tended to be white (81.7% vs 77.0%), were more likely to have bone only metastases (18.1% vs 6.4%), less likely to have CNS metastases (2.8% vs 8.2%), and have fewer metastatic sites at diagnosis (49.1% vs 43.2%) than those with HR- MBC. Of patients with HR+ MBC, who were stage I- III at initial diagnosis, 51.3% received adjuvant HT, of which 73.2% received tamoxifen. Median DFI was 48.8 vs 29.4 mo for patients receiving tamoxifen vs an aromatase inhibitor. First-line MBC treatment regimens included: HT only (13.8%); HT + trastuzumab (8.4%); HT + trastuzumab + CT (6.2%); trastuzumab only (6.0%); CT only (11.0%); trastuzumab + CT (53.5%). Analyses of progression-free survival by HR status and first-line treatments (HT only, trastuzumab ± HT or ± CT), are ongoing and will be described. Conclusions: registHER represents the largest dataset of patients with HER2+/HR+ MBC and provides a unique opportunity to characterize treatment patterns, efficacy and safety, and the natural history of this subset of breast cancer patients. [Table: see text]

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The Role of Trastuzumab in Patients with HER2 Positive Small (pT1mi/a) Breast Cancers, a Multicenter Retrospective Study

Cancers ◽

10.3390/cancers13225836 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5836

Author(s):

Andrea Villasco ◽

Silvia Actis ◽

Valentina Elisabetta Bounous ◽

Fulvio Borella ◽

Marta D’Alonzo ◽

...

Keyword(s):

Breast Cancer ◽

Recurrence Rate ◽

Disease Free Survival ◽

Disease Recurrence ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Small Breast ◽

Increased Risk

The treatment with adjuvant Trastuzumab in patients diagnosed with HER2+ small breast cancers is controversial: limited prospective data from randomized trials is available. This study aims to measure the effect of Trastuzumab in the early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which are the factors that most affect the prognosis of small HER2+ tumors. One hundred HER2+ pT1mic-pT1a breast cancer patients who were treated in three Turin Breast Units between January 1998 and December 2018 were retrospectively selected and reviewed. Trastuzumab was administered to 23 patients. Clinicopathological features and disease-free survival (DFS) were compared between different subgroups. The primary outcome was the disease recurrence rate. Median follow-up time was 86 months. Compared to pT1a tumors, pT1mic lesions had a higher tumor grade (84% of pT1mic vs. 55% of pT1a; p = 0.003), a higher Ki-67 index (81% vs. 46%; p = 0.007) and were more frequently hormone receptor (HR) negative (69% vs. 36%, p = 0.001). Disease recurrence rate was significantly lower among patients who received adjuvant Trastuzumab (p = 0.02), with this therapy conferring an 85% reduction in the risk of relapse (HR 0.15; p = 0.02). Among the patients who did not receive adjuvant Trastuzumab, the only factor significantly associated with an increased risk of developing a recurrence was the immunohistochemical (IHC) subtype: in fact, HR− HER2+ tumors showed a risk seven times higher of relapsing (HR 7.29; p = 0.003). Adjuvant Trastuzumab appears to reduce the risk of disease recurrence even in small HER2+ tumors. The adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors since they have the highest risk of recurrence, independently from size and grade.

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CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835918818346 ◽

2018 ◽

Vol 10 ◽

pp. 175883591881834 ◽

Cited By ~ 11

Author(s):

Adriana Matutino ◽

Carla Amaro ◽

Sunil Verma

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Breast Cancers ◽

Cyclin Dependent Kinase ◽

Her2 Positive ◽

Hormone Receptor Positive ◽

Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

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Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients

Future Oncology ◽

10.2217/fon.15.34 ◽

2015 ◽

Vol 11 (10) ◽

pp. 1493-1500 ◽

Cited By ~ 5

Author(s):

G Mustacchi ◽

F Puglisi ◽

AM Molino ◽

D Crivellari ◽

C Ghiotto ◽

...

Keyword(s):

Breast Cancer ◽

Observational Study ◽

Cancer Patients ◽

Early Breast Cancer ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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Sonographic Study of Female Pelvic Organs in Breast Cancer Patients Taking Tamoxifen: Clinical Correlation

Journal of Current and Advance Medical Research ◽

10.3329/jcamr.v7i1.46425 ◽

2020 ◽

Vol 7 (1) ◽

pp. 17-23

Author(s):

Rafia Parveen ◽

Shaikh Shofiur Rahman ◽

Taposhi Sarker ◽

Syed Muhammad Baqui Billah ◽

Zakir Hossain Habib

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Endometrial Thickness ◽

Tamoxifen Therapy ◽

Tamoxifen Treatment ◽

Breast Cancer Patients ◽

Group Iii ◽

Group I ◽

Group Ii ◽

Uterine Volume

Background: As most of breast cancer patients are treated with Tamoxifen, different effects of this drug in patients should be evaluated since no such study is carried out in Bangladesh till date. Objective: The purpose of the present study was to evaluate sonographic changes of female genital organs in breast cancer patients treated with Tamoxifen and to correlate these changes with duration of Tamoxifen treatment and gynecological symptoms. Methodology: This randomized double-blind clinical trial was carried out in Delta Medical College Hospital, Dhaka, Bangladesh from May 2017 to April 2018 for a period of one (1) year. The participants were breast cancer patients which were divided into three groups named as group I patients. The patients of these group were on Tamoxifen therapy. The patients of group II were without Tamoxifen therapy. The patients of group III had completed Tamoxifen therapy. All participants underwent ultrasonography. Results: Patients receiving Tamoxifen therapy had significantly more thickened endometrium compared to other groups (26.6% in group I, 5% in group II and3% in group III). Similarly, abnormal sonographic findings and mean uterine volume were higher in group I compared to other two groups. Endometrial thickness and uterine volume showed significant positive correlation with duration of Tamoxifen therapy (p <0.0001). The endometrial thickness and uterine volume greatly increased after two years of Tamoxifen therapy while it was reverse in group III. Gynecological symptoms had no significant relations with sonographic abnormalities and thickened endometrium. Conclusion: Tamoxifen therapy is associated with increased endometrial thickness, uterine volume and abnormal sonographic findings, compared to patients without Tamoxifen or completing Tamoxifen therapy. Journal of Current and Advance Medical Research 2020;7(1): 17-23

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Profiling receptor tyrosine kinase fusions in Chinese breast cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15092 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15092-e15092

Author(s):

Zhonghua Tao ◽

Xichun Hu ◽

Wen-Ming Cao ◽

Jianxia Liu ◽

Ting Li ◽

...

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cancer Patients ◽

Tyrosine Kinases ◽

Breast Cancer Subtype ◽

Stage Iv ◽

Tyrosine Kinase Domain ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB < 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.

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