Inclusion Criteria:

          -  PRE-REGISTRATION INCLUSION CRITERIA

          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
             criteria that is:

               -  A non-nodal lesion is considered measurable if its longest diameter can be
                  accurately measured as >= 1.0 cm with computed tomography (CT) scan, CT component
                  of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
                  and/or

               -  A malignant lymph node is considered measurable if its short axis is > 1.5 cm
                  when assessed by CT scan (CT scan slice thickness recommended to be no greater
                  than 5 mm)

               -  Note: tumor lesions in a previously irradiated area are not considered measurable
                  disease; disease that is measurable by physical examination only is not eligible

          -  Received =< four (4) prior chemotherapy regimens in the metastatic setting

          -  Cohort A one of the following must be true:

               -  Distant disease progression during administration of combination therapy with
                  taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) for
                  metastatic disease

                    -  Note: patients who began treatment with this combination and discontinued
                       taxane-based chemotherapy due to intolerability before distant disease
                       progression are eligible

               -  Distant disease progression during administration or within 180 days of
                  discontinuing combination therapy with taxane based chemotherapy and anti-HER2
                  therapy (trastuzumab or pertuzumab) in the adjuvant disease

                    -  Note: patients who began treatment with this combination and discontinued
                       taxane-based chemotherapy due to intolerability before distant disease
                       progression are eligible

               -  For patient who received taxane based chemotherapy and anti-HER2 therapy
                  (trastuzumab or pertuzumab) in the neo-adjuvant setting and underwent surgical
                  resection of primary breast disease: distant disease progression during or within
                  180 days of discontinuing anti-HER2 therapy (trastuzumab or pertuzumab) in the
                  adjuvant setting

          -  Cohort B (one of the following must be true):

               -  Distant disease progression during administration of combination therapy with
                  endocrine therapy and anti-HER2 therapy (trastuzumab or pertuzumab) for
                  metastatic disease; permissible endocrine therapies include an aromatase
                  inhibitor or fulvestrant

                    -  NOTE: Tamoxifen is not permissible

               -  Distant disease progression during administration of combination therapy with
                  endocrine therapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the
                  adjuvant setting; permissible endocrine therapies include an aromatase inhibitor
                  or fulvestrant

                    -  NOTE: Tamoxifen is not permissible

          -  Willingness to provide mandatory tumor tissue specimens for correlative research

               -  NOTE: If insufficient or no tissue is obtained by the pre-registration biopsy, an
                  archival tissue specimen (preferably from a metastatic site) from procedure
                  performed =< 2 years prior to pre-registration must be available to submit for
                  Central Laboratory review prior to registration

                    -  Exception: If there is no medically safe site for biopsy, Study Chair (Dr.
                       Haddad) may waive this requirement

          -  REGISTRATION INCLUSION CRITERIA

          -  Registration must be completed =< 28 days of pre-registration

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Histological confirmation of HER2-positive advanced breast cancer; HER2+ is defined by
             2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)
             guidelines

          -  For Cohort B only: Histologic confirmation of ERalpha positive disease (>= 1%
             expression)

          -  Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to
             registration)

          -  Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)

          -  Direct bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to
             registration)

          -  Aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver
             involvement) (obtained =< 14 days prior to registration)

          -  Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula
             (obtained =< 14 days prior to registration)

          -  Cardiac ejection fraction (left ventricular ejection fraction [LVEF]) >= 50% by
             echocardiogram =< 28 days prior to registration

          -  Provide written informed consent

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  Negative urine pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

               -  NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required

          -  Patient and his/her partner agree to use adequate contraception after providing
             written informed consent through 3 months after the last dose of TVB-2640, as follows:

               -  For women: Compliant with a medically-approved contraceptive regimen during and
                  for 3 months after the treatment period or documented to be surgically sterile or
                  postmenopausal

               -  For men: Compliant with a medically-approved contraceptive regimen during and for
                  3 months after the treatment period or documented to be surgically sterile; men
                  whose sexual partners are of child-bearing potential must agree to use 2 methods
                  of contraception prior to study entry, during the study, and for 3 months after
                  the treatment period

          -  Willingness to provide mandatory tumor tissue and/or blood specimens for correlative
             research

        Exclusion Criteria:

          -  PRE-REGISTRATION EXCLUSION CRITERIA

          -  Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity

          -  Patients with a history of LVEF decline to below 50% during or after prior trastuzumab
             or other HER2 directed therapy =< 6 months prior to pre-registration

          -  Patients with any class of New York Heart Association (NYHA) congestive heart failure
             (CHF) or heart failure with preserved ejection fraction (HFPEF)

          -  Patients with a history of known coronary artery disease or a myocardial infarction
             within 12 months prior to pre-registration

          -  Patients with persistently uncontrolled hypertension (systolic blood pressure [BP] >
             160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical therapy

          -  Patients with known unstable angina pectoris

          -  Patients with a known history of serious cardiac arrhythmias requiring treatment
             (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)

          -  Patients with a prolonged corrected QT interval (QTc) interval (>= 450 ms)

          -  Leptomeningeal disease or uncontrolled brain metastasis

               -  NOTE: Metastases treated by surgery and/or radiotherapy such that patient is
                  neurologically stable and off steroids >= 4 weeks prior to preregistration are
                  eligible

          -  Failure to recover from acute, reversible effects of prior therapy regardless of
             interval since last treatment

               -  EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at
                  least 3 months since completion of prior treatment

          -  Tumors involving spinal cord or heart

          -  Visceral crisis or lymphangitic spread

               -  NOTE: Visceral crisis is not the mere presence of visceral metastases, but
                  implies severe organ dysfunction as assessed by symptoms and signs, laboratory
                  studies, and rapid progression of disease

          -  Uncontrolled intercurrent non-cardiac illness including, but not limited to,

               -  Ongoing or active infection

               -  Psychiatric illness/social situations

               -  Dyspnea at rest due to complications of advanced malignancy or other disease that
                  requires continuous oxygen therapy

               -  Or any other conditions that would limit compliance with study requirements

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy

               -  NOTE: Patients known to be HIV positive, but without clinical evidence of an
                  immunocompromised state, are eligible for this trial

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  History of myocardial infarction =< 6 months, or congestive heart failure requiring
             use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

          -  Prior history of hypersensitivity, drug or radiation-induced, or other immune-mediated
             pneumonitis

          -  Patient is unable to swallow oral medications or has impairment of gastrointestinal
             (GI) function or GI disease that may significantly alter drug absorption (e.g. active
             inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption
             syndrome); note: concomitant therapy with proton pump inhibitors and/or H2-receptor
             antagonists is permissible

          -  Patient has a history of clinically significant dry eye (xerophthalmia) or other
             corneal abnormality, or if a contact lens wearer, does not agree to abstain from
             contact lens use from baseline through the last TVB-2640 dose

          -  Patients with a history of intolerance to trastuzumab (i.e. a grade 3 or 4 infusion
             reaction) are excluded; Note: patients with a history of mild infusion reaction to
             trastuzumab who have previously been successfully re-challenged after an infusion
             reaction with or without prophylactic medication are allowed

          -  Other invasive malignancy =< 3 years prior to pre-registration

               -  EXCEPTIONS: Non-melanoma skin cancer, papillary thyroid cancer, or
                  carcinoma-in-situ of the cervix which has been adequately treated

               -  NOTE: If there is a history of prior malignancy, patients must not be receiving
                  other treatment for their cancer and the disease must be inactive/stable

          -  REGISTRATION EXCLUSION CRITERIA

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Any of the following therapies prior to registration:

               -  Chemotherapy =< 3 weeks

               -  Immunotherapy =< 3 weeks

               -  Biologic therapy =< 3 weeks

               -  Monoclonal antibodies =< 3 weeks

               -  Radiation therapy =< 2 weeks

               -  CDK 4/6 inhibitors =< 4 weeks

               -  mTOR inhibitors =< 4 weeks