Neoadjuvant Endocrine Therapy in Breast Cancer

Letrozole as Neoadjuvant Treatment in Postmenopausal and Premenopausal Patients With Highly Endocrine Responsive Operable Breast Cancer

The study aimed to compare the duration to complete or partial response (CR/PR) and the overall response rates (ORR) after six months of neoadjuvant endocrine therapy between pre-menopausal group and post-menopausal group with highly endocrine responsive operable mammary carcinoma.

Study Overview

• Status: Completed
• Conditions: Highly Endocrine Responsive Operable Breast Cancer
• Intervention / Treatment: Drug: Letrozole 2.5Mg Tablet; Drug: GnRH analogue

Detailed Description

Estrogen receptor (ER) positive constitutes about 75% of all breast cancer(BC). Neoadjuvant endocrine therapy(NET) plays an important part in primary therapy of the hormone receptor (HR) -positive and HER2 -negative breast cancer. Recent studies revealed that the third-generation aromatase inhibitors (AIs) have superior ORR than tamoxifen in the HR-positive BC post-menopausal patients. The Z1031 trial showed that Letrozole obtained better ORR than the other two AIs anastrozole and exemestane after 16-18 weeks NET, although without any statistically significance.

In spite of these findings, the optimal duration of NET has not been fully elaborated, Although prolonged treatment might further reduce the tumor size. Further clinical benefits were achieved when the period of treatment of neoadjuvant letrozole prolonged more than three to four months. The 2015 St. Gallen International Consensus Conference recommended continuing neoadjuvant therapy in highly hormone-sensitive breast cancer for a minimum of 4-8 months. However, most studies aim to identify the excellent efficacy of the AIs compared with other drugs but not the duration of NET therapy. Antonio et al. suggest that the time to maximum clinical efficacy may be the optimal period of treatment for the patients; And the median time to maximum efficacy was 4.2 months (95% CI, 4.0-4.5). The present study evaluated the time to CR/PR and the ORR after 6 months of NET.

Previous clinical studies investigating NET mainly focused on post-menopausal women, data on pre-menopausal women is still relatively lacking due to the widely perception that more benefit may be achieved from neoadjuvant chemotherapy (NCT) among younger patients. The result of Z1031 trial showed superiority of neoadjuvant of AIs and promoted wider application of AIs as NET in the HR-positive post-menopausal women, and the clinical response rate (CRR) of letrozole was 74.8% after 16-18 weeks of treatment. The combination of AIs and GnRH analogue may be alternative for selected pre-menopausal patients. The STAGE trial showed the overall response rates of anastrozole plus goserelin in pre-menopausal patients was 70.4% after 6 months of NET. However, studies comparing the ORR and optimal duration of NET between pre-menopausal and post-menopausal patients were rare.

The purpose of the our research was to compare the duration to CR/PR and the ORR after 6 months of NET between pre-menopausal and post-menopausal women with highly endocrine responsive operable BC.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510080
      • Minyi Cheng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Females ≥18 years
2. ER-positive (≥50%), PgR-positive (≥50% ), HER2-negative, and previously untreated, non-metastatic primary invasive BC.
3. The tumour size had to be >1 cm.

Exclusion Criteria:

1. male patients;
2. patients with inflammatory breast cancer or distant metastasis;
3. patients who were previously treatment treated with chemotherapy, radiation therapy or prior treatment with AIs or antiestrogens for breast cancer;
4. patients with a second concomitant neoplasm;
5. patients who could not meet the eligibility criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: the postmenopausal; 2.5 mg letrozole every day for six months	Drug: Letrozole 2.5Mg Tablet; letrozole 2.5mg p.o.qd
Experimental: the premenopausal; 2.5 mg letrozole daily along with a GnRH analogue for ovarian suppression, which was administered as an intramuscular injection of 3.75 mg triptorelin every 28 days for 6 months.	Drug: Letrozole 2.5Mg Tablet; letrozole 2.5mg p.o.qd; Drug: GnRH analogue; 3.75 mg triptorelin im. q28d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	overall response rate	six months

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: December 25, 2017
• First Submitted That Met QC Criteria: January 5, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 14, 2018
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Breast Neoplasms Endocrine-responsive Neoadjuvant Duration Letrozole
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: 20170811

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No