Efficacy of Anastrozole and Fulvestrant in Patients With ER Positive, HER2 Negative, Operable Breast Cancer

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole or fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes or by blocking the use of estrogen by the tumor cells. Giving hormone therapy before surgery may be an effective treatment for breast cancer. It is not yet known whether anastrozole is more effective than fulvestrant when given before surgery in treating women with breast cancer. PURPOSE: This randomized phase II trial is studying anastrozole to see how well it works compared with fulvestrant in treating postmenopausal women with stage II or stage III breast cancer that can be removed by surgery.

Sex

Female

DISEASE CHARACTERISTICS:

* Histologically confirmed infiltrating breast adenocarcinoma

  * Large, operable tumor
  * Stage T2 (≥ 3 cm) or T3-T4 (excluding inflammatory disease), N0-N3, M0 disease

    * No bilateral inflammatory breast tumors (T4d \[PEV-2 or PEV-3\])
  * Elston-Ellis grade I or II and mitotic index 1 or 2 (if \< 65 years of age)
* At least 1 embedded and 1 frozen biopsy sample available
* No multifocal or multicentric tumors for which breast conservation cannot be envisaged
* No ErbB2-overexpressing tumors (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive)
* Hormone receptor status:

  * Estrogen receptor and/or progesterone receptor positive tumor (\> 10%) as assessed by IHC

PATIENT CHARACTERISTICS:

* Female
* Postmenopausal
* ECOG performance status 0-2
* ANC ≥ 2,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Total bilirubin ≤ 1.25 times ULN
* AST and ALT ≤ 1.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* No other cancer within the past 10 years, except basal cell skin cancer or previously treated carcinoma in situ of the cervix
* No uncontrolled cardiac pathology, including any of the following:

  * Angina pectoris
  * Congestive cardiac insufficiency
  * Myocardial infarction within the past 3 months
* No known history of hemorrhagic diathesis
* No known allergy to the study drugs or their excipients
* No congenital galactosemia, glucose malabsorption syndrome, or lactase deficiency
* No chronic somatic or psychiatric illness with pejorative prognosis
* No geographical, social, or psychiatric condition that would preclude study compliance and follow-up schedule
* No individual deprived of liberty or placed under the authority of a tutor

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy, hormonal therapy, or any targeted treatment for the breast tumor
* At least 2 weeks since prior hormone replacement therapy for menopause
* No concurrent long-term anticoagulation treatment
* No concurrent participation on another therapeutic trial involving an experimental molecule

• RESULTLerebours F, Rivera S, Mouret-Reynier MA, Alran S, Venat-Bouvet L, Kerbrat P, Salmon R, Becette V, Bourgier C, Cherel P, Boussion V, Balleyguier C, Thibault F, Lavau-Denes S, Nabholz JM, Sigal B, Trassard M, Mathieu MC, Martin AL, Lemonnier J, Mouret-Fourme E. Randomized phase 2 neoadjuvant trial evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: Results of the UNICANCER CARMINA 02 French trial (UCBG 0609). Cancer. 2016 Oct;122(19):3032-40. doi: 10.1002/cncr.30143. Epub 2016 Jun 17. PMID 27315583
• DERIVEDLerebours F, Pulido M, Fourme E, Debled M, Becette V, Bonnefoi H, Rivera S, MacGrogan G, Mouret-Reynier MA, de Lara CT, Pierga JY, Breton-Callu C, Venat-Bouvet L, Mathoulin-Pelissier S, de la Motte Rouge T, Dalenc F, Sigal B, Bachelot T, Lemonnier J, Quenel-Tueux N. Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials. Br J Cancer. 2020 Mar;122(6):759-765. doi: 10.1038/s41416-020-0733-x. Epub 2020 Jan 31. PMID 32001832
• DERIVEDLiang X, Briaux A, Becette V, Benoist C, Boulai A, Chemlali W, Schnitzler A, Baulande S, Rivera S, Mouret-Reynier MA, Bouvet LV, De La Motte Rouge T, Lemonnier J, Lerebours F, Callens C. Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609). J Hematol Oncol. 2018 Oct 11;11(1):124. doi: 10.1186/s13045-018-0670-9. PMID 30305115