- Age

- Family history

- Early menarche

- Late menopause

- Nulliparity

- Older age at first live childbirth

- Prolonged HRT

- BrCa 1 and BrCa 2 mutations

- Obesity

- Alcohol

- Painless lump --> solitary, unilateral, solid, hard, irregular, and non-mobile

- Less comonly: nipple discharge, retraction, dimpling

Breast mass:  self detected, screening mammography, most commonly benign

Further evaluate:  Mammogram and/or ultrasound

Diagnosis:  Biopsy, cell types may be lobular or ductal, invasive or non-invasive

I and II:  Localized to breast and/or axillary lymph nodes, smaller tumor sizes, operable and curable

III:  Larger tumor and/or many lymph nodes involved, may or may NOT be immediately operable, curable most of the time

IV:  Also called M1, or advanced breast cancer.  Cancer spread to distant sites (bone, liver, brain).  Not curable, goal is palliation and prolongation of survival

Node status: Most important predictor

Tumor Size:  The smaller the better

Estrogen +/- progesterone receptor status of tumor:  ER+ tumors are generally less aggressive than ER- (which would be a bad risk factor to have)

HER2+ receptor overexpression:  HER2+ is a negative risk factor

Surgery: Can be lumpectomy or masectomy (remove entire breast), equivalent survival

Radiation:  XRT or RT, given after lumpectomy

Systemic Therapy:  Means IV or PO therapy.  Hormonal therapy given depends on pre- or post-menopausal, but ONLY to ER+ patients

Chemotherapy:  Adjuvant is after surgery, neoadjuvant is before surgery

LCIS: Lobular carcinoma in situ.

- No treatment OR

- Surgery and tamoxifen for risk reduction

DCIS:  Ductal carcinoma in situ

- Surgery (lumpectomy or masectomy) THEN

- radiation (only in lumpectomy) THEN

- Tamoxifen for 5 years

- Tumor size > 1cm AND/OR

- Node + (positive)

*Note: Systemic means hormonal therapy and/or chemotherapy

If you are a stage I-III breast cancer patient, what kind of systemic adjuvant therapy should you receive if you have.....

ER+ expression

ER- expression

HER2+ expression

HER2- expression

ER+ --> Hormonly therapy plus chemotherapy

ER- --> Chemotherapy only

HER2+ --> Chemo will include the anti-HER2 targeted therapy Trastuzumab

HER2- --> Chemotherapy will NOT include Trastuzumab

Name the treatments for the following breast cancer characteristics.......

- Estrogen fuels certain breast cancers

- Estrogen can be produced in different places

- In pre-menses, estrogen is produced in the ovaries

- In post-menses, estrogen is produced in peripheral sites such as adrenal glands and body fat

- In post-menses, aromatase inhibitors inhibit the aromatase enzyme that converts testosterone to estrogen in peripheral sites

- Tamoxifen

- Estrogen receptor modulator; antagonist on breast but agonist on endometrium and bone

- Dose is 20mg qd x 5 years

- SE: Endometrial cancer, rate of 38% in ages > 50, DVT/PE, hot flashes and vaginal discharge, cataracts, good for bone

- Avoid strong 2D6 inhibitors (Sertraline, fluoxetine, paroxetine); NOT inhibitors include (Citalopram, escitalopam, venlafaxine)

- Do NOT give Tamoxifen at same time as chemo; If chemo needed give Tamoxifen AFTER

- Aromatase inhibitors are first line:

- Anastrozole (Arimidex)

- Letrozole (Femara)

- Exemestane (Aromasin)

- SE: Myalgia/arthralgia, bone loss, hot flashes, dryness or discharge.  Counsel on calcium supplements

- AI x 5 years OR

- Tam x 2-5 years then AI x 2-5 years (at least 5 years total therapy)

Tamoxifen:

More --> Endometrial cancer, vaginal bleeding/discharge, irregular menses, DVT/PE, cataracts

Less --> Bone loss, cardiac risk

Aromatase Inhibitors:

More --> Arthralgias/myalgias, diarrhea, osteoporosis/bone loss, cardiac risk

Less --> DVT/PE, NO endometrial cancer

- Cyclophosphamide

- Anthracyclines (Doxorubicin) --> have shown benefit in node positive disease

- Taxanes (Paclitaxel or Docetaxel) --> have shown benefit in node positive disease

- Trastuzumab (in HER2+ only)

*New nonanthracycline regimens (TC and TCH) now also recently an option

AC --> Anthracycline + Cyclophosphamide

Dose Dense AC --> Anthracycline + Cyclophosphamide followed by dose dense paclitaxel with pegfilgrastim support

TAC --> Taxane + Anthracycline + Cyclophosphamide (usually pegfilgrastim support)

TC --> Taxane + Cyclophosphamide 

AC-TH --> Anthracycline + Cyclophosphamide + Taxane with concurrent Trastuzumab

TCH --> Taxane + Carboplatin then Trastuzumab

Adverse Effects:  Myelosuppression, n/v, mouth sores, alopecia, rare cases of leukemia, rare cardiotoxicity, don't give with Trastuzumab

Monitoring: 

- CBC's

- LFT's

- Premedicate with anti-emetics

- check heart function

- Good mouth care

- Max cumulative dose of 450-550 mg/m2

Side-effects:  Myelosuppression, bladder irritation/hemorrhagic cystitis, amenorrhea, nausea, alopecia

Monitoring:  Increase oral fluid intake to prevent cystitis, CBC, antiemetics before chemo to prevent N/V

- Paclitaxel, Docetaxel

Side-effects:  hypersensitivity rxns, peripheral neuropathy, alopecia, myalgia/arthralgia, myelosuppression, fatigue, mouth sores, nausea

**Docetaxel more myelosuppression, skin reactions, fluid retention/edema, nail changes, less infusion reactions**

Monitoring:  Infusion rxns/premedication.
Paclitaxel - Dexamethasone 20mg IV, H1/2 blocker, infusion time

Docetaxel  - Dexamethasone 8mg BID x 3 days, start day before chemo

Check:

- CBC's

- LFT's

- Joint/muscle pain, neuropathy

- Monoclonal antibody directed against the HER2 protein

- HER2+ only

- Adverse effects:  Infusion reactions (rare, first dose given over 90 minutes), fever/chills, cardiotoxicity (rare)

- Monitoring:  Vital signs for infusion reactions, MUGA scans q4-6 months for cardiac function

Neutropenia - Some adjuvant chemo regimens in breast cancer fulfill criteria for use of G-CSF

- >20% risk of febrile NTP and curable cancer

- Examples:  DD AC and TAC

- G-CSF = filgrastim or pegfilgrastim

Anemia - Erythropoietin (Epoeitin) not recommened in breast cancer

- Chemotherapy is first line in ER- tumors

- First line in ER+ tumors ONLY if very fast growing/symptomatic

- In this stage, sequential single agents should be used, with the EXCEPTION of targeted combos

Anthracycline (doxorubin or liposomal dox-Doxil®)

Taxanes inc Paclitaxel albumin-bound (Abraxane®)

Capecitabine

Vinorelbine

Gemcitabine

Other: Ixabepilone

CAF/FAC

AC

AT (dox/docetaxel)

Docetaxel/capecitabine

GT:Gemcitabine/paclitaxel

Paclitaxel/bevacizumab

Ixabepilone +/- capecitabine