Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer
Brief Summary: Trial for the optimization of risk assessment and therapy success prediction in patients with early breast cancer by the use of biomarkers in advance to therapy decision-making to personalize therapies.


Options:
A: 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
B: Inclusion Criteria:

* Pathologic confirmation of invasive breast cancer
* Stage: Clinical T1 \>/= 1.0 cm, T2 or T3, N0-3, M0
* HER2 negative
* ER and PgR status by immunohistochemistry must be known. ER positive patients are allowed if physicain has determined neoadjuvant chemo is appropriate.
* Life expectancy greater than six months
* Use of an effective means of contraception is required

Exclusion Criteria:

* Pregnant or breastfeeding
* Prior anthracycline or platinum based therapy
* Prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy
* Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast-conserving treatment and hormonal therapy for DCIS or invasive cancer
* Peripheral neuropathy of any etiology that exceeds grade 1
* Significant hearing loss
* Renal dysfunction
* Use of other investigational or study agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
* Uncontrolled intercurrent illness
* Any condition that would prohibit administration of corticosteroids
* Uncontrolled diabetes
* Pre-existing medical condition that would represent toxicity in excess of grade 1 as measured by CTCAE (unless not considered medically significant by the physician)
* Known HIV positive individuals on combination antiretroviral therapy
C: 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
D: 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

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

Answer: A