Invasive Breast Cancer
Conditions
Brief summary
The purpose of this research study is to better understand the reasons why or why not breast cancers are destroyed by standard chemotherapy. This information will be used to develop new and better cancer therapies.
Interventions
None listed
Sponsors
Mayo Clinic
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Histological confirmation of invasive breast cancer. * Confirmation of breast cancer lesion ≥ 1.5 cm in size by any clinical (physical examination measurement) or radiographic criteria (mammogram, ultrasound or MRI) in the ipsilateral breast. * Note: Benign breast disease, LCIS or DCIS in the contralateral breast is allowed. Contralateral invasive breast cancer is allowed if disease is of clinically lower stage and the higher stage lesion will be the study lesion for all biopsies and tissue samples. * Note: Disease in axilla only is not eligible. * Note: Patients that have a contraindication or inability to have an MRI may still be enrolled on study and not participate in the MRI at any of the study specific time points. * Note: For patients with bilateral disease the higher clinical stage disease will be the study lesion that will undergo study biopsies and tissue samples from surgery and the contralateral lesion will NOT undergo research biopsies and tissue samples. * Men or women who are to begin neoadjuvant chemotherapy for treatment of Stage I-III Her 2 negative breast cancer with paclitaxel followed by either the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) or the combination of doxorubicin and cyclophosphamide (AC). OR Men or women who are to begin neoadjuvant chemotherapy for treatment of Stage I-III Her 2 positive breast cancer with paclitaxel followed by either the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) or the combination of doxorubicin and cyclophosphamide (AC). MC1137 Trastuzumab will be given concurrently with the taxane portion and can be given concurrently with FEC (but not AC) at the discretion of the medical oncologist. * Note: Her2 positive disease is defined to be: HER2 score of 3+ by IHC or HER2 gene amplification by FISH. * Provide informed written consent. * Willing to return to Mayo Clinic in Rochester, MN, Mayo Clinic in Arizona, or Mayo Clinic in Florida for imaging correlative, surgery, and follow-up. * Willing to provide blood samples for correlative research purposes. * Willing to provide tissue samples for correlative research purposes. * ECOG Performance Status ≤ 2.
Exclusion criteria
* Receiving any investigational agent which would be considered as a treatment for the primary neoplasm. * Other active malignancy ≤ 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. * Note: If there is a history or prior malignancy, they must not be receiving any other treatment for their cancer. * Patients who are not planning to receive neoadjuvant chemotherapy. * Biopsy proven Stage IV disease. * Patients who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA From the Germline and Breast Tumor for the Identification of Novel Somatic Changes Within Gene and Gene Pathways. | 1 year 3 months | To obtain DNA from the germline and breast tumor for the identification of novel somatic changes within gene and gene pathways that are potentially druggable in men or women with breast cancer undergoing a standard neoadjuvant paclitaxel (with or without trastuzumab), followed by a standard anthracycline containing regimen (e.g. doxorubicin and cyclophosphamide) for breast cancer. We will report the median frequency and range of mutations observed for 30 mutated genes of interest. |
| Frequency of Known Tumor Mutations for Which Current Drug Therapies Already Exist. | 1 year 3 months | To determine the number of patients with one or more known tumor mutations for which current drug therapies already exist (e.g. BRAF, C-KIT, EGFR mutation, KRAS, PTEN, PI3K). |
| Association Between Breast Cancer Events and Patient-derived Xenografts (PDX) Engraftment | 1 year 3 months | Using breast cancer tissue obtained prior to chemotherapy in all patients and following the completion of chemotherapy (in patients with residual tumors \> 2 cm or residual nodal disease), to develop tumor xenograft cell lines for mechanistic and functional studies to determine whether mutations identified are associated with the malignant phenotype and response to associated drugs which target the gene and/or pathways. The breast cancer relapse rate of patients that received pre-NAC PDX engraftment will be reported. |
| Somatic Alterations Identified Are Associated With Pathologic Complete Response to Therapy. | 1 year 3 months | To determine whether somatic alterations identified above are associated with pathologic complete response (pCR) to therapy. The number of patients experiencing a pCR with one or more somatic alterations will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | 1 year 3 months | Assess the association between changes in 99mTc-sestamibi uptake and pathologic response following neoadjuvant chemotherapy (MCR participants only). Sensitivity, specificity, positive predictive value, and negative predictive value after NAC at MRI and MBI will be reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy | 132 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Desire go to immediately to surgery | 3 |
| Overall Study | Disease Progression | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy |
|---|---|
| Age, Customized Age <30 | 2 Participants |
| Age, Customized Age 30-39 | 21 Participants |
| Age, Customized Age 40-49 | 36 Participants |
| Age, Customized Age 50-59 | 40 Participants |
| Age, Customized Age 60-69 | 24 Participants |
| Age, Customized Age 70+ | 9 Participants |
| Clinical N-stage N0 | 56 Participants |
| Clinical N-stage N1 | 69 Participants |
| Clinical N-stage N2 | 4 Participants |
| Clinical N-stage N3 | 3 Participants |
| Clinical T-stage T1 | 12 Participants |
| Clinical T-stage T2 | 55 Participants |
| Clinical T-stage T3 | 60 Participants |
| Clinical T-stage T4 | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Region of Enrollment United States | 132 participants |
| Sex: Female, Male Female | 132 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Association Between Breast Cancer Events and Patient-derived Xenografts (PDX) Engraftment
Using breast cancer tissue obtained prior to chemotherapy in all patients and following the completion of chemotherapy (in patients with residual tumors \> 2 cm or residual nodal disease), to develop tumor xenograft cell lines for mechanistic and functional studies to determine whether mutations identified are associated with the malignant phenotype and response to associated drugs which target the gene and/or pathways. The breast cancer relapse rate of patients that received pre-NAC PDX engraftment will be reported.
Time frame: 1 year 3 months
Population: 113 patients had pre-NAC PDX engraftment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | Association Between Breast Cancer Events and Patient-derived Xenografts (PDX) Engraftment | 13.6 percentage of patients |
Primary
DNA From the Germline and Breast Tumor for the Identification of Novel Somatic Changes Within Gene and Gene Pathways.
To obtain DNA from the germline and breast tumor for the identification of novel somatic changes within gene and gene pathways that are potentially druggable in men or women with breast cancer undergoing a standard neoadjuvant paclitaxel (with or without trastuzumab), followed by a standard anthracycline containing regimen (e.g. doxorubicin and cyclophosphamide) for breast cancer. We will report the median frequency and range of mutations observed for 30 mutated genes of interest.
Time frame: 1 year 3 months
Population: Pre-NAC tumor and germline sequencing data were generated for 122 patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | DNA From the Germline and Breast Tumor for the Identification of Novel Somatic Changes Within Gene and Gene Pathways. | 3 mutations |
Primary
Frequency of Known Tumor Mutations for Which Current Drug Therapies Already Exist.
To determine the number of patients with one or more known tumor mutations for which current drug therapies already exist (e.g. BRAF, C-KIT, EGFR mutation, KRAS, PTEN, PI3K).
Time frame: 1 year 3 months
Population: Pre-NAC tumor and germline sequencing data were generated for 122 patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | Frequency of Known Tumor Mutations for Which Current Drug Therapies Already Exist. | 78 Participants |
Primary
Somatic Alterations Identified Are Associated With Pathologic Complete Response to Therapy.
To determine whether somatic alterations identified above are associated with pathologic complete response (pCR) to therapy. The number of patients experiencing a pCR with one or more somatic alterations will be reported.
Time frame: 1 year 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | Somatic Alterations Identified Are Associated With Pathologic Complete Response to Therapy. | 44 Participants |
Secondary
99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy.
Assess the association between changes in 99mTc-sestamibi uptake and pathologic response following neoadjuvant chemotherapy (MCR participants only). Sensitivity, specificity, positive predictive value, and negative predictive value after NAC at MRI and MBI will be reported.
Time frame: 1 year 3 months
Population: Only patients underwent both MRI and MBI after NAC
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Sensitivity for MRI | 69.4 percent |
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Positive predictive value for MRI | 81.4 percent |
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Negative predictive value for MRI | 71.4 percent |
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Sensitivity for MBI | 58.9 percent |
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Positive predictive value for MBI | 84.6 percent |
| Individuals Aged 18 or Older With Stage I-III BC Who Plan to Undergo Neo-adjuvant Chemotherapy (NAC) | 99mTc-sestamibi Uptake and Pathologic Response Following Neoadjuvant Chemotherapy. | Negative predictive- value for MBI | 54.9 percent |