Neoadjuvant therapy is given to breast cancer patients whose cancers are relatively large or
have spread to lymph nodes or both. The primary goal of this treatment is to prevent the
cancer from coming back (recurring) elsewhere in the body, but if it makes the cancer in the
breast and lymph nodes shrink it might be easier to remove. This could allow a patient to
have a lumpectomy instead of a mastectomy and reduce the number of lymph nodes that the
surgeon has to remove. In some cases, the neoadjuvant therapy works so well that it kills
all of the cancer in the breast and lymph nodes. This is referred to as a pathologic
complete response (pCR). Patients who achieve a pCR have a much lower risk of the cancer
recurring elsewhere in their bodies.
Investigators aren't sure which chemotherapy drugs work best with the HER2-targeted drugs,
and what combination of these drugs causes the fewest side effects.Thus, this study has two
1. To find out if treatment with wPCbTP, weekly paclitaxel and carboplatin given with
trastuzumab and pertuzumab every 3 weeks, leads to as many pCRs as TCHP in patients
with HER2-positive breast cancer, but has fewer side effects.
2. To find out if HER2-positive patients whose cancers are not responding well after 12
weeks of wPCbTP get a better response when they are switched to a
doxorubicin-containing regimen called AC for 4 cycles (8-12 weeks).
1 Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available
from needle or incisional biopsy (excisional biopsy not permitted) for ER, PR and HER2
2. Resectable - clinical stage I (only with T=2.0 cm), IIA-IIIA - T2 N0-T3N0 or T1-3
N1-N2a - or unresectable - clinical stage IIIB-C - T4 or N2b-3 - disease. No evidence of
M1 disease. Pretreatment clinical stage will be recorded by the treating physician.
3. Breast tumor measuring at least 1 cm in greatest dimension by ultrasound or MRI;
patients without measurable disease in the breast (TX) by imaging studies are eligible if
they have measurable disease (a node measuring at least 1 cm along its short axis, and
histologically confirmed to contain metastatic disease) in the axilla.
4. HER2+, defined by either IHC 3+ or amplification of the HER2 gene by FISH analysis
(ratio >2.0 or >6 HER2 targets per cell; patients with equivocal HER2 testing, 2+ by IHC
with a FISH ratio of <2.0 and 4-6 HER2 signals per nucleus, are not eligible).
5. Patients with multiple foci of invasive cancer in the same breast are eligible if any
single lesion meets the above size criteria and all sampled lesions are histologically
similar and HER2+ (whether radiographically detected lesions separate from the target
lesion are sampled for histologic evaluation is left to the discretion of the treating
physicians). The presence of DCIS or LCIS in either breast will not render a patient
ineligible. Patients with a small focus of invasive cancer detected in the contralateral
breast (clinical T1a/bN0) are eligible, whether the contralateral tumor in HER2+ or HER2-,
while patients with a more advanced cancer in the contralateral breast are not eligible;
in patients with a small focus of invasive cancer in the contralateral breast only the
histologic response in the breast containing the target lesion will be considered in
determining the patient's pathologic response.
6 It is recommended that patients have a pretreatment echocardiogram or MUGA scan with an
LVEF above the institutional lower limit of normal.
7. Female, age >18, Zubrod PS 0-1. 8. It is recommended that patients have adequate bone
marrow, renal and hepatic function. Examples of this include: ANC > 1000/ul, platelet
count >100,000/ul, HGB> 9.0 g/dl, serum creatinine <1.5 mg/dl or measured creatinine
clearance of >30 ml/min and AST <5 x ULN.
9. Signed informed consent.
1. Prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
2. Patients with congestive heart failure, myocardial infarction, unstable angina
pectoris or arterial thrombotic event within the past 12 months, uncontrolled
hypertension (SBP>160 or DBP>90), uncontrolled or clinically significant arrhythmia,
grade II or greater peripheral vascular disease or prior history of stroke or TIA
(transient ischemic attack).
3. Pregnant and lactating women are not eligible. All patients of reproductive potential
should have a negative pregnancy test at baseline and be advised to use an effective
barrier method of contraception if sexually active during treatment on the study and
for 2 months post the last treatment. Sites will be asked to confirm the patient's
menopausal status at study entry and that premenopausal women had a negative
pregnancy test performed within 7 days of starting treatment, but will not be
required to submit test results.
4. Active non-breast malignancy.
5. Baseline grade >2 peripheral neuropathy
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female