Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency (HRD Patients With Deleterious BRCA1/2 Tumor or Germline Mutation and/or HRD Score High)
Brief Summary: This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive

* paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or
* paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery.

The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen.


Options:
A: Inclusion Criteria:

* Invasive breast cancer, diagnosed by core needle or incisional biopsy (excisional biopsy not permitted)
* The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor (ER) and progesterone receptor (PgR) negative or staining present in =\< 10% of invasive cancer cells by immunohistochemistry (IHC)
* The invasive tumor must be HER2-negative, defined as IHC 0-1+ or with a fluorescent in situ hybridization (FISH) ratio (HER2 gene copy/chromosome 17) of \< 2.0 if IHC 2+
* Clinical stage II-III invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy; patients with inflammatory breast cancer are not eligible; staging to rule out metastatic disease is recommended for clinical stage III patients
* Patients with multicentric or bilateral disease are eligible if the target lesion meets eligibility criteria
* Patient agrees to undergo pretreatment research biopsies
* No prior chemotherapy, hormone therapy, or radiation therapy with therapeutic intent for this cancer
* The target lesion in the breast must be \>= 1 cm, clinically or radiographically; palpable or radiographically measurable axillary adenopathy will be recorded but will not serve as measurable disease for the primary endpoint; patients with axillary disease only (no identifiable tumor in the breast that is \>= 1 cm on physical exam or radiographic study) are not eligible to participate
* Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower gastrointestinal \[GI\] bleeding) within 6 months of registration are not eligible
* No serious or non-healing wound, skin ulcers or bone fracture; no abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; no major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of study
* The following are not considered to be major surgical procedures that would be prohibited in the 28 days prior to, or following study randomization: obtaining the required research needle biopsies; placement of a radiopaque clip to localize a tumor or tumors for subsequent surgical resection; placement of a port for central venous access; fine needle aspiration of a prominent or suspicious axillary lymph node; needle biopsy of a clinically or radiographically detected lesion to rule out metastatic disease; or pretreatment sentinel lymph node sampling
* No baseline neuropathy grade \>= 2
* Zubrod performance status 0-1
* Pregnant or nursing women are not eligible; all women of reproductive potential must have a negative pregnancy test at baseline and agree to use an effective, non-hormonal method of contraception during the entire period of treatment on the study
* Patients with congestive heart failure are not eligible, nor are patients with myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack (TIA) within the past 12 months, uncontrolled hypertension (systolic blood pressure \[SBP\] \> 160 or diastolic blood pressure \[DBP\] \> 90), uncontrolled or symptomatic arrhythmia, or grade II or greater peripheral vascular disease
* Patients must have a pretreatment multi gated acquisition (MUGA) scan or echocardiogram with a left ventricular ejection fraction (LVEF) above the institutional lower limit of normal
* Granulocytes \> 1,000/mcl
* Platelets \> 100,000/mcl
* Total bilirubin =\< 1.5 x upper limits of normal
* Calculated or measured \> 30 ml/min
* Urine protein =\< 1+ or urine protein to creatinine (UPC) ratio \< 1

  * Patients discovered to have \>= 2+ proteinuria at baseline must undergo a 24-hour urine collection that must demonstrate \< 1 g of protein/24 hr, or UPC ratio \< 1 to allow participation in the study
* Serum alanine aminotransferase (ALT) =\< 2.5 x upper limits of normal
* Serum beta human chorionic gonadotropin (HCG) negative (for women of child bearing potential)
* Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN)

  * Unless patient is on therapeutic doses of warfarin; if so, the patient must have an INR =\< 3 on a stable dose of warfarin, must have not active bleeding or pathologic condition that is associated with a high risk of bleeding
B: Inclusion Criteria:

1. Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures.
2. Complete baseline documentation must be sent to GBG Forschungs GmbH.
3. Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
4. Centrally confirmed negative HER2-status. Centrally confirmed estrogen and progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is defined as ≥1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio ≥2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization.
5. Centrally confirmed tumor Homologous Recombinant Deficiency score (tBRCA positive/mutated and/or HRD high). Patients with known gBRCA and/or tBRCA status can be enrolled prior to the central test results available.
6. Tumor lesion in the breast with a palpable size of \> 2 cm or a sonographical size of \>1 cm in maximum diameter. If the tumor is not detectable with sonography mammography assessment can be considered. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
7. Patients must be in the following stages of disease:

   * cT2 - cT4a-d or
   * cT1c and cN+ or cT1c and pNSLN+ or
   * cT1c and ER-neg and PR-neg or
   * cT1c and Ki67\>20% In patients with multifocal or multicentric breast cancer, the largest lesion should be measured and at least one lesion has to meet the above criteria
8. Age \> 18 years.
9. Karnofsky Performance status index ≥ 80%.
10. Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution.
11. Laboratory requirements:

    Hematology
    * Absolute neutrophil count (ANC) ≥2.0 x 109 / L and
    * Platelets ≥100 x 109 / L and
    * Hemoglobin ≥10 g/dL (≥ 6.2 mmol/L) Hepatic function
    * Total bilirubin ≥1.5x UNL and
    * ASAT (SGOT) and ALAT (SGPT) ≥1.5x UNL and
    * Alkaline phosphatase ≥2.5x UNL.
12. Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
13. Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (≥21 days, and in no case exceed 6 weeks prior to randomization) (Note MRI/ CT scan may be used as an alternative imaging technique). In case of high risk according to guidelines: chest X-ray (PA and lateral) or as an alternative breast MRI/CT, abdominal ultrasound or CT scan or MRI, and bone scan in case of high risk for primary metastasis according to guidelines. In case of positive bone scan, bone X-ray or CT scan is mandatory. Other tests may be performed as clinically indicated.
14. Male or female patients
15. Patients must be available and compliant for central diagnostics, treatment and follow-up.

Exclusion Criteria:

1. Prior chemotherapy for any malignancy within 5 years.
2. Prior radiation therapy for breast cancer within 5 years.
3. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
4. Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
5. Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
6. Known or suspected congestive heart failure (\>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP \>140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
7. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
8. Patients currently in an institution by order of jurisdictional or governmental grounds.
9. Currently active infection.
10. Definite contraindications for the use of corticosteroids.
11. Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
12. Concurrent treatment with:

    * chronic corticosteroids unless initiated \> 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent).
    * sex hormones. Prior treatment must be stopped before study entry.
    * other experimental drugs or any other anti-cancer therapy.
13. Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
14. Prior use of a PARP-Inhibitor
C: Inclusion Criteria:

* Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
* Histologically confirmed unilateral primary invasive carcinoma of the breast
* Clinical T1 - T4 (except inflammatory breast cancer)
* All clinical N (cN)
* No clinical evidence for distant metastasis (M0)
* Known HR status and HER2 status (local pathology)
* Tumor block available for central pathology review
* Performance Status ECOG \<= 1 or KI \>= 80%
* Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
* Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
* The patient must be accessible for treatment and follow-up

Additional Inclusion criteria for patients receiving chemotherapy:

* Laboratory requirements for patients receiving neoadjuvant chemotherapy (within 14 days prior to induction treatment):

  * Leucocytes \>= 3.5 x 10\^9/L
  * Platelets \>= 100 x 10\^9/L
  * Hemoglobin \>= 10 g/dL
  * Total bilirubin \<= 1 x ULN
  * ASAT (SGOT) and ALAT (SGPT) \<= 2.5 x UNL
  * Creatinine \<= 175 µmol/L (2 mg/dl)
* LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment)

Exclusion Criteria:

* Known hypersensitivity reaction to the compounds or incorporated substances
* Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin or pTis of the cervix uteri
* Non-operable breast cancer including inflammatory breast cancer
* Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
* Concurrent treatment with other experimental drugs. Participation in another interventional clinical trial with or without any investigational not marketed drug within 30 days prior to study entry
* Male breast cancer
* Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
* Breast feeding woman
* Sequential breast cancer
* Reasons indicating risk of poor compliance
* Patients not able to consent

Additional Exclusion Criteria for patients receiving chemotherapy:

* Known polyneuropathy ≥ grade 2
* Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease
* Uncompensated cardiac function
* Inadequate organ function including:

  * Leucocytes \< 3.5 x 10\^9/l
  * Platelets \< 100 x 10\^9/l
  * Bilirubin above normal limits
  * Alkaline phosphatase \>= 5 x UNL
  * ASAT and/or ALAT associated with AP \> 2.5 x UNL
D: Inclusion Criteria:

* Histologically confirmed invasive cancer of the breast
* Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)
* No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
* Age ≥18 years
* ECOG performance status 0-1
* Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
* Non-pregnant and non-lactating
* No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible.
* Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL Screening Consent)
* Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites metastasis
* Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F
* Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN, AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine \< 1.5 x institutional ULN
* No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear imaging or echocardiography) must by ≥ 50%
* No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
* Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (\<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™)
* Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2)

Exclusion Criteria:

* Use of any other investigational agents within 30 days of starting study treatment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Answer: B