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6 months versus 12 months of HER2-targeted therapy after a complete response to preoperative chemo for early HER2+ breast cancer

ShortStop-HER2: Shortened Duration of Adjuvant Therapy in Patients With Early-Stage HER2+ Breast Cancer Who Achieve pCR After Neoadjuvant Chemotherapy With HER2 Blockade

Phase 3 Interventional Alliance for Clinical Trials in Oncology · NCT06876714

This tests whether 6 months of HER2-targeted therapy works as well as 12 months for people with early HER2+ breast cancer who had a pathologic complete response after preoperative chemotherapy with trastuzumab.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1524 (estimated)
Ages18 Years and up
SexAll
SponsorAlliance for Clinical Trials in Oncology Academic / other
Drugs / interventionstrastuzumab, pertuzumab, chemotherapy, radiation
Locations631 sites (Phoenix, Arizona and 630 other locations)
Trial IDNCT06876714 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized trial enrolls patients with early-stage HER2-positive breast cancer who achieved a pathologic complete response (no residual invasive disease) after neoadjuvant chemotherapy that included trastuzumab. Participants are randomized to receive either 6 months or 12 months of combined HER2-targeted therapy (trastuzumab with or without pertuzumab) in the neo/adjuvant setting. The co-primary endpoints are non-inferiority for recurrence-free survival and comparison of quality of life (FACT-B) at 12 months, with additional safety and subgroup analyses including cardiac monitoring by echocardiography or MUGA. Secondary outcomes include overall survival, rates of grade 3+ adverse events, locoregional and CNS recurrence, and RFS in key subgroups by stage and hormone receptor status.

Who should consider this trial

Good fit: People (women and men) with early-stage (clinical T1c–T3, N0–N1 except T3N1) HER2-positive breast cancer who had no residual invasive disease (pCR) after neoadjuvant chemotherapy that included trastuzumab and who have known hormone receptor status are ideal candidates.

Not a fit: Patients with residual invasive disease after surgery (including residual node-positive disease or T3N1 tumors), HER2-negative tumors, or those who did not receive trastuzumab-based neoadjuvant therapy are unlikely to qualify or benefit from this comparison.

Why it matters

Potential benefit: If 6 months is non-inferior, patients could have shorter treatment with fewer side effects, lower cost, and similar cancer control.

How similar studies have performed: Prior adjuvant duration trials have produced mixed results—some (like PERSEPHONE) supported shorter trastuzumab durations in selected populations, but de-escalation specifically after pCR following neoadjuvant therapy remains relatively under-studied.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stage N0-N1 (except T3N1 tumors, which are not eligible)
* Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) is allowed. Patients with residual isolated tumor cells at surgery are considered node-positive and are not eligible
* HER2+ by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Central pathology review is not required. In cases where there were multiple tumor sites in breast/nodes that had HER2 testing at diagnosis, at least one site must have been HER2+ AND the treating investigator must feel it is in the patient's best interest to be treated as having HER2+ breast cancer
* Known hormone receptor status as defined by ASCO/CAP guidelines. Estrogen receptor (ER) and progesterone receptor (PR) of any values are allowed. Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR
* If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts (including the requirement that at least one biopsied site on each side must have been HER2+)
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patients must have received neoadjuvant chemotherapy in combination with trastuzumab with or without pertuzumab for a minimum of 12 weeks. All chemotherapy must have been completed preoperatively

  * Patient must complete a minimum of 12 weeks of coverage with trastuzumab and a maximum of 24 weeks in the combined neoadjuvant and adjuvant setting prior to trial registration. Trastuzumab may have been administered either weekly or once every 3 weeks (q3weeks). (For purposes of this eligibility criterion, a single dose of q3week trastuzumab would provide 3 weeks of coverage; a single dose of once a week (q1week) trastuzumab would provide 1 week of coverage. If a q3week dose of trastuzumab were administered and then the subsequent dose was delayed for any period of time, that would still count as 3 weeks of coverage.)
  * Administration of endocrine therapy for treatment of this breast cancer is allowed prior to trial registration. If a patient received prior breast cancer endocrine therapy (eg tamoxifen or aromatase inhibitor) for DCIS or preventive indication, and endocrine therapy is indicated for treatment of their current breast cancer, then prior endocrine therapy must have been stopped \> 12 months prior to registration on this protocol
  * No use of investigational anti-cancer agents at time of registration
* Patient must register within 14 weeks of final surgery
* Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:

  * Breast surgery: Total mastectomy with grossly negative margins (in the opinion of the surgeon there is no disease grossly at the margins) or breast-conserving surgery with histologically negative margins (no ink on tumor, including DCIS) unless those margins are anterior at the skin or posterior at the chest wall and no additional margin re-excision can be performed
  * Lymph node surgery: Lymph node surgery must have been performed and can include sentinel lymph node biopsy, targeted axillary dissection, or axillary dissection, at the discretion of the breast surgeon
* Adequate radiation: Patients who completed breast-conserving surgery (i.e. lumpectomy) must have received or plan to receive adjuvant radiation. If breast-conserving surgery was performed but patient will not be receiving breast radiation, the patient is not eligible. Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation) are not eligible

  * Adjuvant radiation can be given on study, and in this case is encouraged to be given concurrently with adjuvant HER2-directed therapy, per investigator discretion
  * Targeting of the regional nodal basins will be at treating investigator discretion
* Not pregnant and not nursing, because this study involves agents with known teratogenic potential. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test should be performed prior to receiving HER2-directed therapy according to local standard practice
* Adequate hepatic, renal and bone marrow function to receive adjuvant HER2-directed therapy in the opinion of the treating investigator. There are no specific required laboratory values for eligibility
* No stage IV (metastatic) breast cancer
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* No history of any prior (ipsilateral \[ipsi-\] or contralateral) invasive breast cancer. Prior DCIS is allowed
* No evidence of recurrent disease following preoperative therapy and surgery
* Patients living with HIV who are healthy and deemed by their medical team to have a low risk of AIDS-related illnesses are included in this trial. Patients with Hepatitis B or Hepatitis C virus who are healthy and deemed by their medical team to meet all other enrollment criteria are included in this trial.
* Patients with inadequate cardiac function on most recent assessment of left ventricular ejection fraction (LVEF) are not eligible for this trial. Inadequate cardiac function is defined as LVEF \< 50% on echocardiogram (echo) or multiple-gated acquisition (MUGA)
* No history of grade 3 or 4 toxicity related to trastuzumab. If pertuzumab is planned to be given on trial, patient must also have no history of grade 3-4 toxicity related to pertuzumab
* No contraindication to receipt of further HER2-directed therapy
* No patients with severe, uncontrolled systemic disease that may interfere with planned trial therapy.

Exclusion Criteria:

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Where this trial is running

Phoenix, Arizona and 630 other locations

+581 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Early Stage Breast Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.