Lead Investigator: Fei Ma, Peking Union Medical College
Title of Proposal Research: The impact of human epidermal growth factor receptor 2-low (HER2-low) Expression on the Efficacy of endocrine therapy in Hormone Receptor-positive/HER2-Negative (HR+/HER2-) Breast Cancer
Vivli Data Request: 8856
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Breast cancer is the most common malignancy among women, with over 2,260,000 newly diagnosed cases and nearly 685,000 deaths worldwide annually. Based on the presence of certain proteins in the cancer cells, called human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR), breast cancer can be classified into four subtypes which are used to determine the correct treatment and which predict the patients expected outcomes.
A test called the ImmunoHistoChemistry (IHC) is used to determine a patient’s HER2 status. If the test is 0 to 1, it’s considered HER2-negative. If the score is 1+ to 2+, it’s considered low. A score of 3+ is considered HER2-positive. Patients with low levels (IHC test 1+ to 2+) of the HER2 protein in their cancer cells are classified as having HER2-low breast cancer, which accounts for 45-55% of breast cancer patients, and is less likely to benefit from conventional HER2-targeting drugs. Recently, a new generation of drugs which target HER2, called antibody-drug conjugates (ADC), which can specifically target and kill cancer cells, have been shown to be effective in HER2-low breast cancer.
HER2-low breast cancers are more diverse in nature than HER2+ cancers, and are often Hormone Receptor-positive (HR+) tumors. This means that they have receptors on the cancer cells for the hormones estrogen (ER), or progesterone (PR). These cancers may be treated with hormone therapy, but signals exchanged between the HER2 and hormone receptor proteins are thought to contribute to HR+ tumours not responding as well to hormone therapy as HER2-zero tumours.
A previous analysis of four clinical trials of 2,310 HER2-negative breast cancer patients found that HER2-low breast cancers have shown significantly longer survival compared with HER2-0 (those with an IHC test of 0). However, some studies revealed no statistically significant prognostic differences between the two subgroups.
Currently, it still remains unclear whether HER2-low breast cancer should be considered as a distinct biological subtype compared to HER2-0. In terms of treatment, the therapeutic strategies for HER2-low metastatic breast cancer (MBC, cancer which has spread to other sites in the body) is mainly determined by HR status. In the HER2-low cancers, there is less HER2 per cell than in HER2+ cancers, and hence there may be less cross-talk between the hormone receptors and HER2, and they may therefore respond better to hormone therapy.
To date the clinical impact of the HER2-low expression on the response to hormone therapy in patients with breast cancer remains controversial. This study aims to evaluate the relationship between HER2-low expression and clinical outcomes in HR+/HER2- breast cancer patients who received hormone therapy, and will hopefully help clinicians select personalized treatment strategies for HR-positive HER2-low breast cancer patients.
We will analyze existing clinical trial data from multiple studies to investigate the impact of HER2-low expression on the efficacy of hormone therapy in HR+/HER2- breast cancer patients. This design enables us to efficiently evaluate a large sample size and obtain meaningful insights from diverse populations. Additionally, we will also conduct subgroup analyses to explore potential differences in treatment efficacy based on other relevant factors, such as age, race, and menopausal status.
We believe that our design and methods will provide effective data support for our research objectives and make valuable contributions to the clinical management and treatment strategies of breast cancer.
Requested Studies:
A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed With Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in The MA.17 Study)
Data Contributor: Project Data Sphere
Study ID: NCT00754845
Sponsor ID: MA17R
A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25 mg Daily), Letrozole (2.5 mg), or Anastrozole (1 mg) in Postmenopausal Women With Clinical Stage II and III Estrogen Receptor Positive Breast Cancer
Data Contributor: Project Data Sphere
Study ID: NCT00265759
Sponsor ID: ACOSOG-Z1031
Phase III Trial of Tamoxifen Alone vs. Tamoxifen Plus Radiation Therapy for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
Data Contributor: Project Data Sphere
Study ID: NCT00003857
Sponsor ID: RTOG-98-04
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY
Data Contributor: Pfizer Inc.
Study ID: NCT01942135
Sponsor ID: A5481023
Phase II Study to Evaluate the Efficacy and Tolerability of Fulvestrant 250mg, 250mg (Plus 250mg Loading Regimen) and 500mg in Postmenopausal Women With ER +ve Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy
Data Contributor: AstraZeneca
Study ID: NCT00305448
Sponsor ID: D6997C00004
Endocrine Therapy With or Without Anti-VEGF Therapy: A Randomized, Phase III Trial of Endocrine Therapy Alone or Endocrine Therapy Plus Bevacizumab (NSC 704865) for Women With Hormone Receptor-Positive Advanced Breast Cancer
Data Contributor: Project Data Sphere
Study ID: NCT00601900
Sponsor ID: NCI-2009-00477
A phase II, double-blind, placebo controlled, randomised study to assess the efficacy and safety of ZD6474 in combination with Arimidex™ vs. Arimidex alone in patients with hormone sensitive (ER+ve and/or PR+ve) tumours as 2nd line treatment for advanced breast cancer (ABC)
Data Contributor: Sanofi
Study ID: D4200C00045
Sponsor ID: D4200C00045
Phase II Study to Evaluate the Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg in Postmenopausal Women With ER +ve Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy
Data Contributor: AstraZeneca
Study ID: NCT00313170
Sponsor ID: D6997C00006
A Randomized, Open-label Study of the Effect of Herceptin Plus Arimidex Compared With Arimidex Alone on Progression-free Survival in Patients With HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT00022672
Sponsor ID: BO16216
A Randomized, Two-Arm, Open-Label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab Plus an Aromatase Inhibitor in First Line Patients With HER2-Positive and Hormone Receptor-Positive Advanced (Metastatic or Locally Advanced) Breast Cancer
Data Contributor: Roche
Study ID: NCT01491737
Sponsor ID: MO27775
PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6 INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINE TREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN
Data Contributor: Pfizer Inc.
Study ID: NCT00721409
Sponsor ID: A5481003
A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 3 STUDY OF PD-0332991 (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE
Data Contributor: Pfizer Inc.
Study ID: NCT01740427
Sponsor ID: A5481008