P1-12-15: Adjuvant Trastuzumab Effect on HER2−Positive Breast Cancers According to Hormonal Receptor (HR) Status: Crosstalk between ER and EGFR/HER2 Pathway May Prevent Trastuzumab from Improving Outcomes in HER2−Positive and HR-Positive Breast Cancers.

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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A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

Journal of Solid Tumors ◽

10.5430/jst.v7n2p28 ◽

2017 ◽

Vol 7 (2) ◽

pp. 28

Author(s):

Gregory A. Vidal ◽

Namratha Vontela ◽

Mary Chen ◽

Julie M. Ryder ◽

Struti Sheth ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Breast Conservation ◽

Breast Cancers ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Skin Reactions ◽

Grade 3

Background: The use of HER2 targeting therapy has revolutionized the treatment of HER2 positive breast cancers. Here, we investigate whether a sequential approach to dual HER2 blockade of lapatinib followed by trastuzumab will result in improved clinical outcomes.Methods: This was a single institution, open label, single arm, phase II trial in women with HER2 positive breast cancer. Volunteers were treated with sequential neoadjuvant doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) for 4 cycles followed by docetaxel (100 mg/m2) concurrent with lapatinib (1,250 mg) (TL) daily for 21 days for four cycles before definitive surgery. The primary end point was pathologic complete response (pCR).Results: The study accrued only 21 of the 71 planned patients from 2/28/2007 to 5/25/2010. All patients (100%) experienced down staging. The pCR rate was 41% (7/18). 11 patients had tumor size of T3 or greater, 3 of which experienced pCR and only 1 underwent breast conservation (lumpectomy). The most common hematologic AE (all grades) was anemia 17/21 (81%). There were no incidences of grade 3 or 4 anemia. 10 of 21 (48%) patients experience a non-hematologic grade 3 AE. The most common non-hematologic AEs (all grades) were irregular menses 20/21 (95%) and hand-foot-skin reactions 20/21 (95%). No increase cardiac abnormalities were noted. The DFS at data cut off was 87.5%.Conclusion: The provocative pCR and DFS results in this high risk locally advanced patient population should be viewed with caution given results of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation study (ALTTO) clinical trial.

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HER2-positive early breast cancers: What proportion are receiving adjuvant trastuzumab therapy? A multicenter audit.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.668 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 668-668 ◽

Cited By ~ 1

Author(s):

S. Marla ◽

J. Cardale ◽

D. J. Dodwell ◽

A. Skene ◽

O. Gojis ◽

...

Keyword(s):

Breast Cancers ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Trastuzumab Therapy

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O-39 HER2 positive early breast cancers: What proportion are receiving adjuvant Trastuzumab therapy? A multicentre audit

European Journal of Cancer Supplements ◽

10.1016/j.ejcsup.2010.06.040 ◽

2010 ◽

Vol 8 (6) ◽

pp. 14-15

Author(s):

S. Marla ◽

J. Cardale ◽

D.J. Dodwell ◽

A.I. Skene ◽

O. Gojis ◽

...

Keyword(s):

Breast Cancers ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Trastuzumab Therapy

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Human epidermal growth receptor-2 overexpressing early operable primary breast cancers in older (≥70 years) women: Biology and clinical outcome in comparison with younger (<70 years) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11608 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11608-e11608

Author(s):

Binafsha Manzoor Syed ◽

Andrew R. Green ◽

Dal Morgan ◽

Ian O. Ellis ◽

Kwok-Leung Cheung

Keyword(s):

Clinical Outcome ◽

Older Women ◽

Clinical Information ◽

Biological Characteristics ◽

Breast Cancers ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Primary Surgery ◽

Epidermal Growth

e11608 Background: There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of HER2 positive tumors in older women. This study aimed to analyse their biological characteristics and compare them with their younger counterparts from a single centre with long-term clinical follow-up. Methods: Over 37 years (1973-2010), 1,758 older (≥70 years) women with early operable (<5cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray (TMA) analysis using immunohistochemistry. Comparison was made with data from a well-characterised younger (<70years) series (N=1,711) treated between1986 - 1998 (before adjuvant trastuzumab became standard) in our institution. Thirty-nine (7.6%) and 140 (8.2%) patients from the older and younger series respectively (p=0.56) had HER2-positive tumours. Results: See Table. Conclusions: The HER2 positive tumours in older women showed relatively less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy as compared to the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated. [Table: see text]

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High recurrence risk and use of adjuvant trastuzumab in patients with small, HER2-positive, node-negative breast cancers

International Journal of Clinical Oncology ◽

10.1007/s10147-011-0269-4 ◽

2011 ◽

Vol 17 (2) ◽

pp. 131-136 ◽

Cited By ~ 14

Author(s):

Akiyo Horio ◽

Takashi Fujita ◽

Hironori Hayashi ◽

Masaya Hattori ◽

Naoto Kondou ◽

...

Keyword(s):

Recurrence Risk ◽

Positive Node ◽

Breast Cancers ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Node Negative

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

QJM ◽

10.1093/qjmed/hcab103.013 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Atef Youssef Riad ◽

Azza Mohammed Adel Alkhateeb ◽

Mohammed Reda Kelany ◽

Mohammed Al-Saeed Sakran Ali Al-Shater

Keyword(s):

Breast Cancer ◽

Progression Free Survival ◽

Breast Cancers ◽

Breast Cancer Patients ◽

University Hospitals ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Group I ◽

Group Ii ◽

The Impact

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 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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