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Abemaciclib plus drug combination in women with early-stage hormone‑positive HER2‑negative breast cancer: phase II study to reduce chemotherapy and surgery

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The trial focuses on patients with HR+/HER2− Early Breast Cancer, which means the tumor grows in response to hormones and does not have excess HER2 protein. These cancers are also described as estrogen receptor–positive and HER2-negative. After an initial tissue sample (biopsy), a gene test called Oncotype DX is used to predict how likely the cancer is to benefit from chemotherapy. The study compares a hormone‑blocking approach that includes the oral drugs exemestane, anastrozole or letrozole together with the targeted medicine abemaciclib against the usual chemotherapy regimen that may contain doxorubicin, epirubicin, paclitaxel or cyclophosphamide. Hormone‑blocking treatment is also called endocrine therapy and works by lowering the level of hormones that can help the tumor grow.

The purpose of the study is to find out whether many patients can safely skip chemotherapy and have less extensive surgery, known as surgical de-escalation. In practice, this means that instead of a full mastectomy, some patients might have a breast‑conserving surgery, and instead of removing many lymph nodes (axillary lymph node dissection) they might only need a sentinel lymph node biopsy, which checks the first few nodes where cancer could spread.

Participants first have a biopsy to confirm the cancer and to run the gene test. A multidisciplinary team reviews the test result and decides whether the patient will receive the hormone‑blocking regimen with the targeted drug or the standard chemotherapy. The chosen treatment is given before surgery (called neoadjuvant, meaning “before the operation”). After the pre‑surgery treatment, the surgeon performs the planned operation, and patients are followed for recovery and any side effects.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Enrollment and Baseline Evaluation

    You sign the informed consent form and become a study participant.

    The study team collects your medical history, performs physical examinations, and obtains imaging and a tissue sample from the breast tumor.

    The tissue sample is sent for the Oncotype DX test, which analyzes the tumor’s genetic profile.

  2. Step 2

    Treatment Decision by Multidisciplinary Team

    A group of doctors reviews the Oncotype DX result and other clinical information.

    Based on the result, the team recommends either neoadjuvant endocrine therapy (NET) plus abemaciclib or standard neoadjuvant chemotherapy (NCT).

    You are informed of the recommended plan and the reasons for it.

  3. Step 3

    Start of Neoadjuvant Endocrine Therapy Plus Abemaciclib

    You take one oral hormone‑blocking tablet each day: either anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg.

    You also take abemaciclib 300 mg by mouth each day.

    You continue these medicines daily until the day of surgery, as directed by the study team.

    Regular clinic visits are scheduled to monitor your blood counts, liver function, and any side effects.

  4. Step 4

    Start of Neoadjuvant Chemotherapy (Comparator Arm)

    You receive chemotherapy drugs through an intravenous (IV) line:

    ‑ Doxorubicin hydrochloride 60 mg/m² infusion,

    ‑ Epirubicin hydrochloride 90 mg/m² infusion,

    ‑ Paclitaxel 80 mg/m² infusion,

    ‑ Cyclophosphamide 600 mg/m² injection.

    Each drug is given on the days specified by the study protocol, usually in repeated cycles every few weeks.

    You attend the infusion center for each treatment and have blood tests and examinations before every cycle.

  5. Step 5

    Ongoing Monitoring and Quality‑of‑Life Assessment

    During the neoadjuvant phase you complete questionnaires such as EORTC QLQ‑C30, EORTC QLQ‑BR42, and EORTC QLQ‑FA12 to report your quality of life.

    The study team records any side effects using the CTCAE v6.0 grading system, which classifies side effects from mild to severe.

    Additional imaging studies may be performed to evaluate tumor response.

  6. Step 6

    Surgery

    After completing the assigned neoadjuvant treatment, you undergo breast surgery.

    The type of surgery (breast‑conserving surgery or mastectomy, and sentinel‑node biopsy or axillary dissection) follows the plan that was recommended before treatment, but may be de‑escalated if the tumor has responded well.

    Pathology results are examined to determine whether a complete response was achieved.

  7. Step 7

    Post‑Surgical Follow‑Up

    You attend follow‑up visits at 6 months and 12 months after surgery.

    During these visits the study assesses progression‑free survival (whether the cancer has returned or spread) and repeats quality‑of‑life questionnaires.

    Any additional adjuvant therapy (treatment given after surgery) is decided based on the pathology findings and study protocol.

Who can join the trial?

16 criteria

  • Female, age 18 years or older
  • Adequate blood, kidney, and liver function – meaning normal levels of white blood cells, platelets, hemoglobin, creatinine (kidney waste), and liver enzymes as checked by blood tests
  • Normal kidney function – defined by a serum creatinine level ≤1.5 times the upper normal limit or a calculated creatinine clearance ≥50 mL/min (a measure of how well the kidneys filter waste)
  • Normal liver function – defined by a total bilirubin level ≤1.5 × upper normal limit (bilirubin is a substance the liver processes), AST and ALT enzymes ≤3 × upper normal limit, and alkaline phosphatase ≤2.5 × upper normal limit; people with mild Gilbert’s syndrome (a harmless condition that slightly raises bilirubin) are allowed if bilirubin is not too high
  • Not pregnant and must agree to use effective non‑hormonal birth control (such as condoms, diaphragm with spermicide, or abstinence) from the time of the pregnancy test until after surgery; hormonal methods like pills, injections, or hormonal IUDs are not allowed
  • Menopausal status must be known – whether you are pre‑menopausal (still having periods) or post‑menopausal (periods stopped), based on age, menstrual history, or lab tests if needed
  • Willing to have breast surgery after completing the planned pre‑surgery (neoadjuvant) treatment
  • Willing to give blood and tumor samples for study purposes, including a special genetic test called Oncotype Dx that helps predict how the cancer may behave
  • Primary, histologically confirmed diagnosis of invasive breast carcinoma – meaning a tissue sample has shown that cancer cells have invaded surrounding breast tissue
  • Estrogen‑receptor (ER) positive tumor – at least 10 % of the cancer cells show receptors for the hormone estrogen (detected by a lab test called immunohistochemistry); any amount of progesterone receptor is acceptable
  • HER2‑negative tumor – the cancer cells do not have excess HER2 protein, as determined by standard testing guidelines
  • Stage II to IIIB disease according to the AJCC TNM classification, with no distant metastases (cancer spread to other organs), except possible small nodes in the internal mammary chain found during a sentinel node procedure
  • Candidate to receive neoadjuvant chemotherapy – a multidisciplinary tumor board (a group of cancer specialists) has recommended chemotherapy before surgery
  • Not eligible for immediate breast‑conserving surgery but may become eligible if the tumor shrinks with treatment, and not a candidate for sentinel lymph node removal because the nodes are already clinically positive
  • ECOG Performance Status 0‑1 – meaning you are fully active (0) or able to do light work but not physically strenuous activity (1)
  • Ability to swallow oral medications

Who cannot join the trial?

11 criteria

  • Distant metastases (stage IV) or stage IIIC breast cancer – the cancer has spread far beyond the breast or is very advanced.
  • Having an active systemic infection, such as a bacterial infection needing intravenous (IV) antibiotics, a fungal infection, or a viral infection like HIV or active hepatitis B or C.
  • Known contraindications (medical reasons not to use the study drug) or an allergic reaction (hypersensitivity) to the study medication or its ingredients.
  • Having inflammatory breast cancer or a locally‑advanced, inoperable breast cancer that cannot be removed by surgery.
  • Having had a previous invasive breast cancer on the same side (ipsilateral) at any time.
  • Having another current or past invasive cancer, except for very specific cancers that were treated well, such as skin basal or squamous cell carcinoma, melanoma in situ, non‑invasive cancers of other organs, certain early‑stage thyroid, cervical, endometrial, or ovarian cancers, or a non‑breast invasive cancer diagnosed at least five years ago with no return.
  • A history of serious cardiovascular disease, including uncontrolled chest pain (angina), very high blood pressure (≥ 180/110 mm Hg), uncontrolled diabetes, shortness of breath at rest (dyspnea), need for long‑term oxygen, advanced heart failure (NYHA class III or IV), fainting due to heart problems, dangerous heart rhythm problems (ventricular arrhythmia, such as ventricular tachycardia or ventricular fibrillation), or sudden cardiac arrest.
  • Being pregnant or breastfeeding (lactating); breastfeeding must be stopped before joining the study.
  • Having any serious or uncontrolled medical condition that could make participation unsafe, such as interstitial lung disease, severe shortness of breath needing oxygen, severe kidney problems (renal impairment with estimated creatinine clearance < 30 ml/min), major stomach or small‑bowel surgery, Crohn’s disease, ulcerative colitis, or chronic diarrhea of grade 2 or higher.
  • Having had major surgery within the past 14 days before starting the study.
  • Receiving an experimental treatment in another clinical trial within the last 30 days (or the time it takes for the drug to leave the body, whichever is longer) or currently being enrolled in another research study that is not compatible with this trial.
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Investigated drugs

  • Exemestane

    is an oral medicine that blocks the enzyme aromatase, which helps lower the amount of estrogen in the body. In this trial it is used as part of hormone therapy before surgery to try to shrink the tumor and reduce the need for chemotherapy.

  • Abemaciclib

    is a pill taken by mouth that blocks proteins called CDK4 and CDK6, which cancer cells need to grow. It is being tested together with hormone therapy to see if it can replace chemotherapy for some patients with early breast cancer.

  • Anastrozole

    is an oral aromatase‑inhibitor that reduces estrogen levels. It is given before surgery as hormone therapy, helping to control tumor growth without the need for chemotherapy.

  • Letrozole

    is another oral aromatase‑inhibitor that lowers estrogen in the body. In the study it is used as a hormone treatment before surgery to shrink the tumor and possibly avoid chemotherapy.

  • Doxorubicin

    is a chemotherapy drug given through an IV infusion. It works by damaging the DNA of cancer cells, stopping them from dividing. In the trial it is used as a standard chemotherapy option to compare with the experimental hormone‑based treatments.

  • Epirubicin

    is an IV chemotherapy medication similar to doxorubicin. It interferes with cancer cell DNA, preventing tumor growth. It serves as a comparator chemotherapy in the study.

What is already known about the treatment

  • Exemestane

    This is a film‑coated tablet taken by mouth, usually once a day. It is an approved aromatase inhibitor that is widely used to treat hormone‑sensitive breast cancer. It works by stopping the body from making estrogen, which helps slow the growth of tumors that need estrogen. It belongs to the class of steroidal aromatase inhibitors.

  • Doxorubicin

    Given as a solution for intravenous infusion, this drug is administered through a vein over a short period. It is a well‑known chemotherapy agent that has been used for many years to treat various cancers, including breast cancer. It attacks cancer cells by inserting itself into DNA and preventing the cells from copying their genetic material, leading to cell death. It is classified as an anthracycline antibiotic.

  • Abemaciclib

    This medication is taken as an oral tablet, usually twice daily. It is an FDA‑approved CDK4/6 inhibitor used for hormone‑positive breast cancer, often together with hormone therapy. It works by blocking proteins (CDK4 and CDK6) that tell cancer cells to divide, thereby slowing tumor growth. Its pharmacological class is a cyclin‑dependent kinase 4/6 inhibitor.

  • Epirubicin

    Administered as an intravenous infusion solution, it is injected into a vein during treatment sessions. It is an established anthracycline chemotherapy drug used for breast cancer and other solid tumors. It disrupts DNA function in cancer cells, making it difficult for them to grow and divide. It belongs to the anthracycline class of anticancer agents.

  • Paclitaxel

    This drug is given as an intravenous infusion of a solution that is delivered through a vein. It is a widely used chemotherapy medicine for breast cancer and many other cancers. It works by stabilizing tiny structures inside cells (microtubules), which stops cancer cells from dividing properly. It is classified as a taxane chemotherapy agent.

  • Anastrozole

    Provided as a film‑coated tablet taken orally once daily. It is an approved aromatase inhibitor commonly prescribed for post‑menopausal women with estrogen‑sensitive breast cancer. It reduces estrogen production in the body, which helps slow or stop tumor growth that relies on estrogen. It belongs to the non‑steroidal aromatase inhibitor class.

Investigated diseases

Estrogen receptor‑positive, HER2‑negative breast carcinoma (stage II–IIIB) – This cancer grows in breast tissue and is driven by estrogen but lacks excess HER2 protein. It typically starts as a palpable lump that enlarges within the breast. As it progresses, cancer cells may spread to nearby lymph nodes. In stage II–IIIB, the tumor is larger and may involve the chest wall or skin, though distant spread has not been documented. The disease can continue to expand locally and infiltrate surrounding structures if not addressed.
Trial detailsLast updated 18 Oct 2026
Age18+ yearsPhasePhase IITrial ID2026-525457-37-00Protocol codeVIOLETEstimated enrolment150 patientsSponsorIstituto Di Ricerche Farmacologiche Mario Negri

sourced from the EU Clinical Trials Register and site verification

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