Impact of Neoadjuvant Hormonal Therapy on the Surgical Management of Extensive Ductal Carcinomas in Situ

Mastectomy Clinical Trial

— HORNEO01  

Official title:

Impact of Neoadjuvant Hormonal Therapy on the Surgical Management of Extensive Ductal Carcinomas in Situ

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04666961
• Other study ID #: ICO-2020-06
• Status: Recruiting
• Phase: Phase 2
• Start date: February 3, 2021
• Est. completion date: August 1, 2033

Study information

• Verified date: April 2022
• Source: Institut Cancerologie de l'Ouest
• Contact: Victoire BRILLAUD-MEFLAH, MD
• Phone: 0240679818
• Email: Victoire.brillaud-meflah[@]ico.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ductal carcinoma in situ (DCIS) accounts for approximately 20% of newly diagnosed breast cancer cases. Of these women, 20% require radical management in the form of mastectomy because of the extent of the lesions, which most often manifest as diffuse microcalcifications.

This mutilating surgical management contrasts with the excellent prognosis of this pathology and considerably alters the quality of life of patients.

Neoadjuvant hormone therapy has shown its efficacy in hormone-dependent infiltrating ductal carcinomas and offers the possibility of conservative surgery after hormone therapy.

Adjuvant hormone therapy with Tamoxifen or anti-aromatase drugs has shown its efficacy in the prevention of homo or contralateral recurrence.

The HORNEO 01 trial fits perfectly in the current context of surgical de-escalation of ductal carcinomas in situ. The objective of the study is to evaluate the impact of neoadjuvant hormone therapy on the surgical management of extensive DCIS.

Description:

Description of the modalities for recruiting :

Following screening and discovery of a DCIS, patients are referred to the center for surgical management.

During a standard consultation, the surgeon presents the study to the patient who has been diagnosed with extensive DCIS with an indication for mastectomy. The surgeon provides the patient with the information note and the consent form to participate in the study. Once the consent form is signed by the patient and the investigator, the investigator prescribes a screening test to be performed within 30 days prior to the start of hormone therapy.

Screening assessment includes :

A clinical exam and a breast imaging exam (mammography and breast and axillary ultrasound). In case of a suspicious breast ultrasound image, microbiopsy will be performed to eliminate an infiltrating component.

One or more macrobiopsy. Each biopsied site will be located using an X-ray clip inserted at the time of sample.

A MRI post-macrobiopsy. Research of estrogen receptor expression

Once the investigator has verified and validated all the eligibility criteria, the patient will be included.

Prescriptions for Tamoxifen (non-menopausal patients) or Anastrozole (menopausal patients) are given to patients and dispensed by the center's pharmacy.

Monitoring during treatment :

Patients will benefit from imaging monitoring (Mammography, +/- breast ultrasound, +/- axillary ultrasound, MRI) at 3 months and 6 months during hormonotherapy.

In case of progression observed during treatment, hormone therapy will be stopped and you will then benefit from a mastectomy.

Surgery :

Mastectomy or tumorectomy will be performed according to the tumor response to hormone therapy observed on MRI.

All patients will benefit sentinel node detection. An additional axillary dissection will be performed based on the results of the sentinel node analysis.

Analysis of biomarkers and tumor microenvironment before and after treatment on diagnostic macrobiopsies and on tumorectomy or mastectomy will be performed at Institut de Cancérologie de l'Ouest.

Patients will be seen in postoperative consultation. Adjuvant treatments or re-surgical interventions will be prescribed, carried out, and the patients will be followed up and examined at 6 months after surgery or at the end of adjuvant treatments and then annually for 10 years (with control mammography).

Patients who have had conservative surgery will have an MRI at 6 months from the end of radiotherapy.

All patients will be asked to complete quality of life questionnaires at baseline, 6 and 12 months post-surgery, and annually for 9 years:

EORTC QLQ-C30 (up to 5 years only), Short Form (36) Health Survey questionnaire.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 262
• Est. completion date: August 1, 2033
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Patient = 40 years old

2. Histological diagnosis of ductal carcinoma in situ without infiltrating contingent

3. Clinical T0N0

4. Estrogen receptor positive (OR+) regardless of progesterone receptor (PR) status

5. Indication for mastectomy

6. DCIS visible on MRI performed with clip sequence

7. Effective contraceptive method for women of childbearing age who are sexually active and who have reported sexual activity.

8. Informing the patient and obtaining free, informed and written consent signed by the patient and the investigator.

9. Affiliated patient or beneficiary of the social security system.

Exclusion Criteria:

1. Invasive breast carcinoma

2. Lobular carcinoma in situ

3. pN+ patient

4. Indication for conservative surgery

5. Contraindications to anastrozole or tamoxifen

6. Concomitant treatments that may interact and reduce the efficacy of tamoxifen by interaction with cytochrome CYP2D6.

7. Histologically proven multifocal lesion

8. Contraindication to breast MRI (pace maker, heart valve, metallic implant, neuronal or peripheral stimulator, severe claustrophobia, ...)

9. History of homolateral breast cancer

10. Ongoing contralateral breast cancer

11. Known mutation BRCA1 BRCA2

12. Other cancer in progress at inclusion

13. Pregnant woman, or breastfeeding,

14. Persons deprived of liberty or under guardianship or trusteeship,

15. Impossibility to undergo the medical follow-up of the trial for geographical, social, psychic or psychiatric reasons.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Carcinoma in Situ
• Extensive Disease
• Mastectomy

Intervention

Drug:
• Tamoxifen 20 mg
Tamoxifen will be initiated in non menopausal patients orally for 6 months in a neoadjuvant situation.
• Anastrozole 1Mg Tab
Anastrozole will be initiated in menopausal patients orally for 6 months in a neoadjuvant situation.

Locations

Country	Name	City	State
France	ICO - Site Paul Papin	Angers
France	Institut Bergonie	Bordeaux
France	Institut de cancérologie de Montpellier	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Hopital Saint Joseph	Paris
France	Institut Curie - Site de Paris	Paris
France	Institut de Cancérologie de l'Ouest	Saint Herblain
France	IUCT-O	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Institut Cancerologie de l'Ouest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of neoadjuvant hormonotherapy	% of conservative surgeries performed after hormonotherapy	6 months of hormonotherapy
Secondary	Disease-free survival (DFS)	DFS rates at 5 and 10 years post-surgery	5 and 10 years post-surgery
Secondary	Overall survival (OS)	Survival rates at 5 and 10 years post-surgery	5 and 10 years post-surgery
Secondary	Pathologic Complete Response (pCR)	Pathologic complete response is defined as no residual invasive cancer in the surgical specimen	6 months of hormonotherapy
Secondary	Predictive factors of response	Response is defined by the variation in the diameter of the longest dimension of the target lesion measured by MRI	3 and 6 months of hormonotherapy
Secondary	Quality of Life (Qol)	EORTC QLQ-C30 questionnaire	At baseline, at 6 months and 12 months post-surgery, and then each year for 4 years
Secondary	Quality of Life (Qol)	SF-36 questionnaire	At baseline, at 6 months and 12 months post-surgery, and then each year for 9 years