ER(+) and/or PR(+) by IHC (? % staining or Allred score ? )
Eligible tumor-node-metastasis (TNM) stages include:\r\n* Estrogen receptor (ER) and progesterone receptor (PR) negative (defined as < % staining for ER and PR by IHC): T or T N, T-N-\r\n** Note: Patients with T, Nmi disease are NOT eligible\r\n* ER and/or PR positive (defined as >= % staining for ER and/or PR on IHC): T-N- or TN\r\n** Note: Patients with TN, TN and T, Nmi disease are NOT eligible\r\n* ER and/or PR positive (defined as >= % staining for ER and/or PR on IHC): T-N- or TN\r\n** Note: Patients with TN, TN, TN and T-, Nmi disease are NOT eligible\r\n* The eligibility of neo-adjuvant subjects can be assessed on the basis of clinical (c)TNM or pathologic (yp)TNM; the same eligible TNM combinations apply; patients may be eligible if they meet eligibility requirements at either time point, as long as they do not have T disease prior to therapy
Female and male patients must have histologically confirmed invasive breast cancer that meets the following criteria:\r\n* Clinical stage II-III (American Joint Committee on Cancer [AJCC] th edition) at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed\r\n* ER- and PR- should meet one of the following criteria:\r\n** =< % cells stain positive, with weak intensity score (equivalent to Allred score =< )\r\n** =< % cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< )\r\n* HER negative (not eligible for anti-HER therapy) will be defined as:\r\n** Immunohistochemistry (IHC) , + without in situ hybridization (ISH) HER/neu chromosome  ratio OR\r\n** IHC + and ISH HER/neu chromosome  ratio non-amplified with ratio less than . and if reported average HER copy number <  signals/cells OR\r\n** ISH HER/neu chromosome  ratio non-amplified with ratio less than . and if reported average HER copy number <  signals/cells without IHC\r\n** NOTE: patients that originally present with synchronous bilateral tumors are eligible provided both tumors are TNBC, and at least one of them fulfills the remainder eligibility criteria of the protocol; multifocal or multicentric breast cancers are eligible as long as all tumors fulfill eligibility criteria\r\n** NOTE: patients that have a discrepancy in ER/PR/HER status between original diagnosis and surgical specimen (only applicable if ER/PR/HER status were repeated; repeating it is not mandatory) are not eligible for study participation (i.e. ER/PR/HER has to fulfill above criteria in both scenarios)
Invasive breast cancer is estrogen receptor (ER) positive with an Allred score of ,  or  by local institution standard protocol; if an Allred score is not reported on the diagnostic pathology report, ER positivity in > % cells is eligible; if ER positivity is =< %, the staining intensity (weak, intermediate, strong) is needed to calculate the Allred score to determine eligibility
Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER-.
SAFETY RUN-IN: Patients with hormone-receptor positive breast cancer (ER and/or PR > %), and with HER- positive breast cancer (by means of immunohistochemistry with + indicating positive status or fluorescence in situ hybridization with amplification ratio >= . indicating positive status)
RANDOMIZED PHASE II CLINICAL TRIAL: Women diagnosed with pathologically confirmed triple negative invasive breast cancer, metastatic (locally confirmed immunophenotype negative for all three receptors ER, PR, HER)
RANDOMIZED PHASE II CLINICAL TRIAL: Patients with hormone-receptor positive breast cancer (ER and/or PR > %), and with HER- positive breast cancer (by means of immunohistochemistry with + indicating positive status or fluorescence in situ hybridization with amplification ratio >= . indicating positive status)
Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of >= 
Clinical T-Tc, any N, M invasive ER+ (Allred score of -) and HER negative ( or + by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] negative for amplification) breast cancer, by American Joint Committee on Cancer (AJCC) th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node\r\n* Note: patients with invasive ER+ (Allred Score of -) HER- breast cancer or ductal carcinoma in situ (DCIS) in the contralateral breast the patient are eligible
PIKCA WILD TYPE COHORT (closed //): Clinical T-Tc, any N, M invasive ER+ (Allred score of -) and HER negative ( or + by IHC or FISH negative for amplification) breast cancer, by AJCC th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node\r\n* Note: patients with invasive ER+ (Allred score of -) HER- breast cancer or DCIS in the contralateral breast the patient are eligible
ENDOCRINE RESISTANT COHORT: Clinical T-Tc at diagnosis or screening, any N, M invasive ER+ (Allred score at least  or > % ER positivity) and HER negative ( or + by IHC or FISH negative or equivocal) breast cancer, by AJCC th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node\r\n* Note: patients with invasive breast cancer that is ER positive (pos), HER negative (neg) or equivocal or DCIS in the contralateral breast are eligible; multi-focal diseases are not excluded; the dominant lesion will be followed per protocol
Local testing on the diagnostic core must have determined the tumor to be ER-negative, PgR-negative, and HER-negative by current ASCO/CAP guidelines. (If local testing has determined a tumor to be HER equivocal or to have a borderline ER/PgR status (% IHC staining < % for both) and other eligibility criteria are met, material may be submitted for central testing to determine eligibility.)
Central testing for ER, PgR, and HER will be performed, and the tumor must be determined to be ER-negative, PgR-negative, and HER-negative by current ASCO/CAP Guidelines Recommendations. Material from either the diagnostic core biopsy or the research biopsy can be used for central testing depending on local preferences and standards.
Patients with synchronous bilateral or multicentric HER-negative breast cancer are eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets stage eligibility criteria. All of the other invasive tumors must also be HER-negative by ASCO/CAP Guidelines based on local testing. Central testing to confirm TNBC status is only required for the highest risk tumor.
Histologically confirmed metastatic ER positive (+) and/or PR+ and HER negative (-) breast cancer who are candidates for palbociclib in combination with either letrozole or fulvestrant per treating physician
Part A) Triple-negative disease (ER/PR/HER-negative) and received at least  prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or ER-positive and/or PR-positive/HER-negative disease and received at least  prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting and are no longer a candidate for hormonal therapy (not enrolling new patients);
Part E) ER-positive and/or PR-positive/HER- disease and received no more than  prior non-hormonally-directed or cytotoxic therapy in the MBC setting.
INCLUSION CRITERIA FOR REGISTRATION (HER MUTATION IDENTIFIED BY WASH U GPS LABORATORY): To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed; in addition, ER and/or progesterone receptor (PR) positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER MUTATION IDENTIFIED BY WASH U GPS LABORATORY): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
Newly diagnosed ER-positive, HER-negative breast cancer. ER-positive is defined as ? % immunohistochemical (IHC) staining of any intensity. HER test result is negative if a single test (or both tests) performed show:
Known HER-, ER-positive, or PR-positive breast cancer by local laboratory assessment
Triple negative (ER-/PR-/HER-) (Note: This group of patients must have received at least  and up to  prior chemotherapy regimens in the advanced setting.)
Histologic confirmation of invasive breast cancer with any measures of ER, PR and HERneu
Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER status, or MammaPrint Low, ER negative (<%), any HER status, or MammaPrint Low, ER positive, HER/neu positive by any one of the three methods used (IHC, FISH, TargetPrint)
HER negative and either ER or PR positive tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fulvestrant) and previously treated with at least  chemotherapy containing regimens.
HER positive and ER and PR negative tumors: must have failed at least  regimens containing at least two anti-HER agents (e.g. trastuzumab and pertuzumab).
Have a diagnosis of ER+ breast cancer (defined as ER > % by IHC)
Women diagnosed with pathologically confirmed HER-overexpressing breast cancer, that is locally recurrent, unresectable or metastatic (negative or positive for ER/PR, and positive for HER)
Histologic confirmation of ER+ breast cancer
Patients must have histologically or cytologically confirmed ER and/or PR positive, HER-/neu negative metastatic breast cancer; they can be enrolled in any line of therapy without investigational agents and should have stable disease or a partial response (which can be determined clinically) on current systemic treatment; patients must also have pathologic OR radiographic evidence of bone metastases and >=  CTCs; (Note: the pathology report that is used by the physician to determine diagnosis, will be used to determine patient eligibility; ER and PR status should be available at the time of registration)
Patients with multifocal or multi-centric disease are eligible if the treating clinician has determined the patient should be treated as ER+ and HER- negative
Bilateral breast cancers are allowed if the treating clinician has determined the patient should be treated as ER+ and HER- negative
Known ER, PgR and HER statuses.
History of ER positive (+) (>= % of cells positive on hematoxylin and eosin stain [H&E]), HER negative (?) breast cancer disease, either as a\r\n* History of primary, operable ER+/HER? invasive breast cancer OR\r\n* History of de novo metastatic breast cancer that is ER+/HER?\r\n** Note: HER? (negative) disease defined as one of the following:\r\n*** HER immunohistochemistry (IHC) expression of , + and in-situ hybridization (ISH) non-amplified\r\n*** HER IHC expression of , + and ISH not done\r\n*** HER IHC expression of + and ISH non-amplified\r\n*** IHC not done and ISH non-amplified; Note: supporting documentation such as a pathology report from their primary diagnosis that indicates ER+/Her- invasive breast cancer or a biopsy report of de novo metastatic breast cancer that is ER+/HER? should be submitted through the RAVE database
Central ER determination on pre-registration biopsy completed
Patients with histologically confirmed diagnosis of locally-advanced, inoperable, metastatic and/or treatment-refractory triple negative breast cancer (TNBC). *Treatment refractory disease is defined as the persistence of tumor lesions following at least one intervention that may include chemotherapy, radiation and/or surgery, or any combination thereof. *Patients must have both ER and PR staining < % and be HER-negative. Patients with ER or PR staining of -%, but who have historically been treated as TNBC may also be enrolled. *Patients must not have disease that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
ER+ status
Disease must be ER+ and HER-
Women with previously untreated, unilateral stage II-III breast cancer, ER/PgR/HER negative (ER =< %, PgR =< %, HER -+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] =< .); if clinically negative lymph nodes, tumor size should be minimum . cm and identifiable under office-based ultrasound guidance
Must have ER positive disease with ER/PR report available.
Addition inclusion for Part A (A & A) Has a histological confirmation of either metastatic breast (ER+ve for Arm A, % ER +ve and % HER+ve metastatic breast cancer patients for Arm A) or castrate-resistant prostate cancer
ER+ve tumours defined as ?% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ?
Part E dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER- non-overexpressing breast cancer
Appropriate archival OR current tissue blocks or biopsy specimens to determine ER/PR and APR status.
The tumor specimen obtained at the time of diagnosis used for HER and ER/and PgR testing must also have central testing for PD-L status; patients who are negative or positive are eligible
Confirmed diagnosis of ER-positive, HER-negative advanced breast cancer, not amenable to curative therapy
Head and neck cancer OR metastatic breast for which standard therapy is not curative\r\n* NOTE: Patients with ER/PR positive, HER negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease and no longer be candidates for standard endocrine therapy; patients with HER positive breast cancer irrespective of ER/PR status must have received or no longer be candidates for standard HER directed therapy (i.e., trastuzumab, pertuzumab, trastuzumab emtansine, and lapatinib); patients with ER/PR/HER negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease; ER/PR and HER status are defined by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Patients must have known ER, PR, and HER status defined as either:\r\n* Triple-negative breast cancer, defined as: ER and PR < % by immunohistochemistry, and HER-negative (defined as IHC  or +, or FISH ratio < .)\r\n* Or, inflammatory breast cancer with any ER, PR, HER status
Metastatic or locally-advanced, histologically documented TNBC (absence of HER, ER, and PR expression)
Centrally confirmed hormone-receptor-positive (?% ER and/or PR positive stained cells) and HER-normal (IHC score - or FISH negative (in-situ hybridization (ISH) ratio) <. status) assessed preferably on tissue from post-neoadjuvant residual invasive disease or core biopsy of the breast, or if no other tissue is available the residual tumor of the lymphnode can be assessed. In case of bilateral breast cancer hormonreceptor positivity and HER-normal status has to be centrally confirmed for both sides.
Histological or cytological confirmation of ER+ BC as assessed by a local laboratory using slides, paraffin blocks, or paraffin sample or by medical history: ER+ (confirmed as ER expression more than or equal to % positive tumor nuclei)
definitively treated, stage I/II ER+ breast cancer
Willing to provide tissue samples for ER and retinoblastoma (RB) staining
Primary tumor was negative for ER, PR (cut-off for positivity is >% positive tumor cells with nuclear staining) and negative for Her-neu ( or + on immunohistochemistry and/or normal gene copy number by in-situ hybridization); Central review is not required.
ER-positive tumor, HER-negative breast cancer
Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm the ER+ (>= % nuclear staining) and HER negative status
Documentation of ER positive (? % positive stained cells by local standards) based on the most recent tumor biopsy, unless bone-only disease
ER/PgR negativity to follow local guidelines
Pre and postmenopausal women or men with stage IV estrogen receptor positive (ER+) breast cancer histological or cytological confirmation\r\n* ER-positive tumors\r\n** Progressed after at least one line of hormonal therapy\r\n** Any number of prior chemotherapy in the metastatic setting\r\n** Any number of prior hormonal therapies\r\n* ER-negative tumors\r\n** PD-L low, high or unknown\r\n** Progression after prior PD- or PD-L inhibitors allowed\r\n** HER positive or negative
Confirmed diagnosis of ER positive breast cancer
ER positive breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is ER+ with low expression (H-score [-]).
Confirmed diagnosis of ER positive breast cancer
Concomitant active malignancy other than ER+ breast cancer.
Invasive breast cancer must be estrogen receptor-positive (ER+) in >  % of the cells or ER allred score -; if ER is positive in >= %, the staining intensity (weak, intermediate, strong) is needed to calculate the allred score to determine eligibility; in institutions where ER expression is classified only by < %, -%, and > % cut-offs, > % expression is required for inclusion
ER/PR determination assays performed by IHC methods according to the local institution standard protocol
Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER-) invasive breast cancer, clinical stage I-III at diagnosis (AJCC th edition) based on initial evaluation by physical examination and/or breast imaging prior to study registration. NOTE: ER, PR and HER status will be confirmed by central pathology review prior to randomization. ER and PR will be considered negative if ? % of cells stain weakly positive. HER will be considered negative if scored  or + by immunohistochemistry (IHC) or + by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < . or <  copies per cell.
Participants must have histologically or cytologically confirmed inoperable locally advanced or metastatic ER+ breast cancer; to fulfill the requirement for ER+ disease, a breast cancer must express, by immunohistochemistry (IHC), ER in >= % of cells, on the most recent biopsy; central confirmation of ER status is not required
Tumors are positive for ER, PgR, or both
Patients enrolled based on tumor ER/PR status must have ER/PR status confirmed by the Laboratory of Pathology, National Institutes of Health (NIH); ER/PR status will be determined on a metastatic site, if possible; otherwise, the original site or available tissue will be acceptable
Phase II: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by modified RECIST version ., who progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, fitting in one of the following groups: Group : patients with PIKCA mutated or amplified ER positive (ER+) breast cancer ; Group : patients with endometrial carcinoma (not selected for any molecular status); Group : patients with solid tumors (with the exception of PIKCA mutant/amplified ER+ breast cancer and endometrial carcinoma) harboring PIKCA mutation or amplification/any PTEN status; Group : patients with solid tumors (with the exception of endometrial carcinoma) harboring PTEN loss of function/ PIKCA wild type; Group : non-small cell lung cancer harboring cMET activation and/or EGFR mutation. Up to  lines of chemotherapy allowed in advanced/metastatic setting.
Estrogen receptor (ER)/progesterone receptor (PR) status (ER or PR defined as positive if >= %; ER/PR is defined as negative if %): \r\n* PHASE I: Patients may have ER/PR(+) or negative (-) breast cancer; ER(+) patients must have progression of disease following  prior line of endocrine therapy; progression of disease within  months of adjuvant endocrine therapy will be considered  line of prior endocrine therapy\r\n* PHASE II: Patients must have ER/PR(-) breast cancer
Tumors must express ER positivity by immunohistochemistry (ER expression >% by immunohistochemistry).
Patients who are ER+ and/or PR+ and who are receiving anti-hormone therapy for at least three months may continue to receive such therapy during the course of the trial
ER and/or PR-positive disease. Tumors must be HER-/neu negative or equivocal.
Patients must be ER >= % and HER negative on local testing
Biopsy proven ER/PR positive tumor
HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status.
Confirmed histologic diagnosis of operable HER overexpressing (ER < %, progesterone receptor [PR] < %, and HER + or fluorescence in situ hybridization [FISH] amplified) OR triple negative (ER < %, PR < %, and HER /+ or +/FISH not amplified) OR ER positive invasive ductal breast cancer, including Memorial Sloan Kettering Cancer Center (MSKCC) pathology confirmation
Biopsy-proven PR-positive (sample size [N]=) or PR-negative (N=) invasive breast cancer, as defined by University of Wisconsin (UW) Health Pathology
Histologically confirmed estrogen receptor positive (ER+) breast cancer either from a metastatic biopsy or from a primary breast tumor with imaging evidence of metastatic disease. The pathology report and either () tumor tissue (blocks or unstained slides) or () a photomicrograph of the ER immunohistochemistry (IHC) slide from at least one site of metastatic disease and/or from primary breast cancer must be available for review and analysis.
No or equivocal ER, PR or HER testing performed prior to surgery if biopsy indicates invasive cancer
No or equivocal ER testing performed prior to surgery if biopsy indicates ductal carcinoma in situ
History of ER+ pathology (ER+ may be confirmed from surgery or biopsy of primary breast cancer or lymph nodes, and/or surgery or biopsy of a metastatic site, metastatic biopsy is not required)
Patients who are to be treated with clinically approved or experimental regimens where ER has an important role
Breast cancer from ER+ primary that is seen on other imaging tests; tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease
PHASE II: Women with a first primary ER+, HER-, LN-, breast cancer <  cm immediately after their initial surgical consultation