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Contraceptive Agents, Hormonal

Megestrol acetate 160 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Anastrozole 1 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Letrozole 2.5 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Exemestane 25 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Tamoxifen 20 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Fulvestrant 500 mg intramuscularly (IM) d1, d14, d28 and q28 days until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Megestrol Acetate 160Mg Tablet

Anastrozole 1Mg Tablet

Letrozole 2.5Mg Tablet

Exemestane 25 MG

Tamoxifen 20Mg Tablet

Fulvestrant 500 mg IM d1, d14, d28 and q28 days

Fulvestrant 50Mg Solution for Injection

Renata Obadia, RN

José Bines, MD, PhD

Jason Carroll, PhD

This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors in advanced breast cancer.

Progesterone receptor (PR) expression has been considered a biomarker of oestrogen receptor-α (ERα) activity. This longstanding relationship has been recently challenged and instead of being merely an ERα-induced gene target, PR may be a critical determinant of ERα activity. The functional significance of this steroid receptor crosstalk is regulation of a gene expression program associated with low tumorigenicity; hence, better disease outcome. Genomic alterations in the PR genomic locus seem to be a relatively common mechanism for reduction of PR expression, which may consequently lead to altered ERα chromatin binding and target gene expression patterns that increase breast tumorigenicity and confers a poor clinical outcome. This ERα-PR crosstalk may be directly influenced by many variables, including the relative receptor levels and the hormonal milieu.

ER-positive advanced breast cancer is a heterogeneous group of diseases with considerable variability in outcome to a range of treatments. Prior response predicts the likelihood of subsequent benefit from another endocrine agent and this should be taken into account in the treatment decision process when assessing whether to prescribe a subsequent endocrine therapy. Despite the enormous progress made regarding the elucidation of breast cancer subgroups and their molecular drivers, most information comes from primary tumors. MA lacks cross-resistance and is active after acquired resistance to potent AI. This pilot trial evaluates in vivo MA modulation of steroidal receptors in advanced breast cancer.

A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer

A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

From date of randomization until the date of death from any cause, assessed up to 18 months

Partial response and stable disease for more than 24 weeks, as per RECIST criteria, from date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 18 months

Cancer Research UK Cambridge Institute

Instituto Nacional de Cancer, Brazil

Triptorelin Pamoate

2.5 mg letrozole every day for six months

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.

GnRH analogue

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.

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 title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer	NCT03024580	Breast Neoplasm	Megestrol Aceta... Anastrozole 1Mg... Letrozole 2.5Mg... Exemestane 25 M... Tamoxifen 20Mg ... Fulvestrant 50M...	-	Instituto Nacional de Cancer, Brazil
Neoadjuvant Endocrine Therapy in Breast Cancer	NCT03397537	Highly Endocrin...	Letrozole 2.5Mg... GnRH analogue	18 Years -	Guangdong Provincial People's Hospital
A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer	NCT03024580	Breast Neoplasm	Megestrol Aceta... Anastrozole 1Mg... Letrozole 2.5Mg... Exemestane 25 M... Tamoxifen 20Mg ... Fulvestrant 50M...	-	Instituto Nacional de Cancer, Brazil
A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer	NCT03024580	Breast Neoplasm	Megestrol Aceta... Anastrozole 1Mg... Letrozole 2.5Mg... Exemestane 25 M... Tamoxifen 20Mg ... Fulvestrant 50M...	-	Instituto Nacional de Cancer, Brazil
Neoadjuvant Endocrine Therapy in Breast Cancer	NCT03397537	Highly Endocrin...	Letrozole 2.5Mg... GnRH analogue	18 Years -	Guangdong Provincial People's Hospital

Spots Global Cancer Trial Database for letrozole 2.5mg tablet