Flashcards in 17 Breast Cancer Chan Deck (72):
What are the risk factors for breast cancer?
Age (80% diagnosed at 50 years of age). Race (White > AA > Asians). Genetics (carriers of BRCA-1, BRCA-2 genes). Family history (one 1st degree relative = two-fold increase, two 1st degree relatives = four-fold increase). Presence of atypical hyperplasia (benign breast cancer) = four-fold increase. Exogenous estrogen. Prolonged estrogen stimulation (long menstrual history). Long phases of uninterrupted ovulation. Alcohol consumption. Diet (high fat intake). Obesity and BMI. Lack of physical activity. Smoking is NOT a risk factor for breast cancer
What are the signs and symptoms of breast cancer?
When tumor is detectable, presentation may include: Lump (solitary, unilateral, solid, hard, irregular and non-mobile), Tenderness, swelling or pain, Areas of thickening, distortion, or skin irritation, Nipple pain or discharge (clear fluid = benign; red brown or bloody = suspicious of malignancy), Breast pain (not usually a first symptom)
What are the ABCs of Breast Health?
A = A screening mammography. B = Breast self-examination (BSE). C = Clinical Breast Exam (CBE)
How often should BSE or Breast awareness be done?
Recommended monthly for all high risk women 20 years of age (best 1 week after menstrual period ends or same day each month if no regular periods). Optional for low risk asymptomatic women
How often should women get a Mammography?
Annual screening in women 50 years of age. Controversial in women ages 40-49. Women at high risk (with strong family history) should be evaluated with annual screening starting 10 years younger than when the youngest family member developed breast cancer
When should a CBE be done?
Recommended annually in women 40 years of age. Recommended every 1-3 years in women ages 20-39 years with breast awareness encouraged. Not uniformly recommended. Most beneficial when used with mammography
Breast Tissue Anatomy: What are Lobules?
Breast Tissue Anatomy: What are Ducts?
Milk passages connect lobules/nipple
Breast Tissue Anatomy: What are Stroma?
Fatty connective tissue/ligaments surround ducts, lobules, blood vessels and lymphatic vessels
What are the five types of breast cancer?
Lobular Carcinoma in Situ (LCIS). Ductal Carcinoma in Situ (DCIS). Invasive Lobular Carcinoma (ILC). Invasive Ductal Carcinoma (IDC). Inflammatory Breast Cancer
What is the most common type of breast cancer?
IDC (Invasive Ductal Carcinoma)
Which breast cancer has the worst prognosis?
IDC (Invasive Ductal Carcinoma)
What is the second most common type of breast cancer?
ILC (Invasive Lobular Carcinoma)
What is LCIS (Lobular Carcinoma in Situ)?
NOT a pre-malignant lesion, but a risk factor. Usually involved both breasts (risk of developing breast cancer relatively low)
What are the management options for PRE- and POST-menopausal women with LCIS (Lobular Carcinoma in Situ)?
Tamoxifen 20mg PO QD x5 years (decreases risk by 49%)
What are the management options for POST-menopausal women with LCIS (Lobular Carcinoma in Situ)?
Raloxifene 60mg PO QD x5 years
What is DCIS (Ductal Carcinoma in Situ)?
Consider a pre-malignant lesion and a risk factor (can present as palpable mass, nipple discharge -- red brown or bloody)
What management option can be considered in DCIS (Ductal Carcinoma in Situ)?
Tamoxifen 20mg PO QD x5 years (decreases risk by 37%). Benefit observed w/ ER+ tumor, unknown benefit w/ ER- tumor
How does Inflammatory Breast Cancer present?
Skin of the affected breast is red, feels warm, and may thicken to the consistency of an orange peel. Thought to be d/t inflammation, but is rather caused by spread of cancer cells to lymphatic vessels of the skin
What is the prognosis of Inflammatory Breast Cancer?
Considered an aggressive tumor with poor prognosis
How is a diagnosis of breast cancer made?
Biopsy = ONLY mean to confirm diagnosis. Most common - fine need aspiration biopsy or core needle biopsy (can determine hormonal and HER2 receptor status)
What do the different stages of breast cancer mean?
Stage 1: Localized. Stage 2-3: Lymph node involvement. Stage 4: Metastases to other organ
What does the ER and/or PR Receptor status mean for prognosis?
ER and/or PR positive indicates less aggressive tumors, better prognosis
What does the presence of HER2/neu overexpression mean?
Indicates more aggressive tumor for node (+) and node (-) patients. Better outcome with Doxorubicin containing chemotherapy regimen (decrease in recurrent rates observed with node (+) patients). Dose-intensive (i.e. Dose-Dense Q2week dosing) of Doxorubicin containing chemotherapy may be more effective of HER2 (+), node (+) patients. Predicts clinical response to therapy with Trastuzumab (Herceptin)
What are the treatment options for breast cancer?
Surgery w/ or w/o reconstruction. Radiation therapy (adjuvant (post lumpectomy at completion of chemo), recurrence of metastatic disease as palliation). Pharmacological intervention
What are the different types of pharmacological intervention that can be used?
Chemotherapy (adjuvant and recurrence disease). Targeted immunotherapy (HER2+ tumor). Hormonal therapy (ER+ and/or PR+ tumor)
What is a Modified Radical Mastectomy (MRM)?
Removes entire breast and some axillary (underarm) lymph nodes (ALND). Does NOT usually require XRT post-op
What is a Segmental Mastectomy (Lumpectomy)?
Considered breast conservation surgery. Removes breast tumor and margin of surrounding normal tissue preserving the natural contour of the breast. Used in combination with ALND and XRT. Selection based on tumor size and location
What is Axillary Lymph Node Dissection (ALND)?
Indicated in ALL women with invasive breast cancer undergoing surgery with MRM or lumpectomy. Controversial in women with small tumors and node (-) breast cancer
What is the complication with ALND?
Risk of lymphedema (d/t absence of normal lymphatic drainage) may develop either immediately after surgery, or months to years after surgery
What is radiation therapy for breast cancer like as Adjuvant Therapy (Postoperative)?
Recommended in ALL patients after lumpectomy. Recommended in patients after MRM if presence of extracapsular extension of LN, tumors > 5cm, skin involvement, (+) margins and distant metastases (high risk patients only). Usually done AFTER completion of chemotherapy in patients with increased risk of distant metastases
When is Radiation therapy as Adjuvant therapy (postoperative) controversial?
In patients with small size (<5 cm), node (-), and margin (-) tumors
What is radiation therapy for breast cancer like for Local Recurrence?
Indicated as primary treatment in patients with inoperable tumors or in patients who do not wish to undergo surgery
What is radiation therapy for breast cancer like for metastatic disease?
For palliation of symptoms ONLY
What is Chemotherapy like for breast cancer?
Anthracycline-based or Non-Anthracycline-based regimen, Taxanes-based regimen, etc
What is Hormonal or Endocrine therapy (ER+ and/or PR+) like for breast cancer?
Anti-estrogens or SERMs, GnRH agonists, Aromatase Inhibitors, mTOR Inhibitors (selection dependent on menopausal status)
What is Adjuvant therapy like for HER2 Positive?
Initiate Trastuzumab (Herceptin) weekly or Q3 week dosing. AVOID concomitant administration with Anthracycline agent (Doxorubicin or Epirubicin) d/t increased risk and frequency of cardiac toxicity (can be taken in same cycle, just not administered on the same day)
What is the most common adjuvant chemotherapy treatment?
AC --> Paclitaxel (T). Anthracycline (Doxorubicin) + Cyclophosphamide x4 cycles (21 days each) --> Paclitaxel IV weekly x12 weeks +/- Trastuzumab (HER2+) IV weekly x1 year
Which common adjuvant chemotherapy treatment is used when there is nodal involvement and possible underlying cardio issues?
TC +/- H. Docetaxel + Carboplatin x6 cycles (21 days) +/- Trastuzumab x1 year
Which chemotherapy treatment is used for recurrence or metastatic disease?
Single or combination agents used. In HER2+ disease, initiate therapy with Trastuzumab (Herceptin) in combinations with chemotherapy
What are the common metastatic chemotherapy agents used for treatment?
Paclitaxel (Taxol) Q21 days or Qweekly until progression. Docetaxel (Taxotere) Q12 days or Qweekly until progression. Paclitaxel-Albumin (Abraxane) Q21 days or Qweekly until progression
What are common ADRs with Cyclophosphamide-based regimens?
Moderate emetogenic (require antiemetics w/ 5HT3 receptor antagonist + corticosteroid). Dose-limiting toxicity = Myelosuppression w/ Leukopenia > thrombocytopenia. High dose toxicity = hemorrhagic cystitis, cardiotoxicity
What is the dose limiting toxicity for Anthracycline-based therapy (Doxorubicin or Epirubicin)?
Cardiovascular toxicity. Life-time cumulative doses: Doxorubicin (400-550mg/m2) and Epirubicin (900mg/m2)
Which chemotherapy agents are Vesicant?
Anthracycline-based (Doxorubicin or Epirubicin). Extravasation (or infiltration) can cause severe tissue necrosis
What medication is indicated ONLY in patients who have received a cumulative Doxorubucin dose > 300 and are continuing with Doxorubicin therapy?
Dexrazoxane (Zinecard) -- Cardio-protectant. Dosed 10:1 ratio
What is the dose-limiting toxicity of Taxane-based therapy (Paclitaxel, Cabazitaxel, Docetaxel or Abraxane)
Myelosuppression (Leukopenia). Dose-dependent neuropathy also a problem
What serious reaction is common with Taxanes?
Hypersensitivity to anaphylactic-like reactions. Paclitaxel > Cabazitaxel > Docetaxel. NOT Abraxane
What is done to avoid hypersensitivity reactions with Taxanes?
Pre-medicate with corticosteroid (Decadron and anti-histamines)
Which Taxane agent causes Fluid retention syndrome?
Docetaxel. Dose dependent. Manage by premedicating with Dexamethasone (Decadron) PO BID day before, the day of, and the day after treatment
What are side effects associated with Gemcitabine (Gemzar)?
Hematologic (DLT) - decreased ANC, decreased Plt, decreased Hgb - require dose adjustment. Elevated LFTs
What is the DLT with Vinca Alkaloid (Vinorelbine (Navelbine))?
Hematologic - Decreased: ANC, Hgb. Require dose adjustment
What are cautions with Lapatinib (Tykerb), a TKI?
Decrease LVEF and QTc prolongation. Pulmonary toxicity - Interstitial lung disease (ILD) and pneumonitis
How is Trastuzumab (Herceptin) dosed for metastatic breast cancer?
Initial LD: 4mg/kg is NS 250ml over 90 minutes. MD: 2mg/kg in NS 250ml over 30 minutes. Qweekly until progression. Anti-HER2 monoclonal antibody
According to the NCCN guidelines, what is the preferred 1st line treatment for HER2+ disease in metastatic breast cancer?
Pertuzumab (Perjeta) - Anti-HER2 monoclonal antibody
What are the ADRs associated with Pertuzumab (Perjeta)?
Similar to Trastuzumab; monitor cardiotoxicity (hold if LVEF decreases to < 40% or decreases 40-50% w/ > 10% decrease from baseline)
When is hormonal or endocrine therapy commonly used?
In hormonal receptor (ER and/or PR) positive tumors at all stages of disease AFTER completion of chemotherapy
What are the Antiestrogens used?
Tamoxifen, Toremifene, Fulvestrant
What are the Aromatase Inhibitors or Inactivators used?
Anastrozole, Letrozole, Exemestane
What are the Selective Estrogen Receptor Modulators (SERM) used?
What hormonal therapy is used for PRE-menopausal women?
Tamoxifen for 5 years +/- ovarian suppression (GnRH agonist) or ovarian ablation (surgery or XRT). No further hormonal therapy recommended after 5 years
Why are Aromatase Inhibitors NOT used in pre-menopausal women?
Not active in women with functioning ovaries
What hormonal therapy is used in POST-menopausal women as adjuvant therapy?
Tamoxifen for 2-3 years followed by an AI (Exemestane or Anastrozole) to compelete 5 years of hormonal therapy
What hormonal therapy is used in POST-menopausal women as subsequent therapy?
Everolimus + Exemestane = hormone receptor (+), HER2 (-) metastatic disease
What is the first line antiestrogen used?
Tamoxifen (Soltamox). Used in metastatic, PRE and POST-menopausal, ER (+). Recommend starting POST-chemotherapy
What do the NCCN guidelines say for Tamoxifen?
1st line agent for Adjuvant therapy in Pre- and Post-menopausal women. Subsequent therapy for systemic disease
What are the ADRs with Tamoxifen?
Hot flashes, mild nausea, vaginal discharge, Thromboembolic events (> AI)
What does long term use of Tamoxifen cause?
An increased risk of endometrial hyperplasia, and uterine cancer
What are some DDIs to use caution with Tamoxifen?
DDIs w/ SSRIs (Less w/ Citalopram and Venlafaxine)
What is Fulvestrant (Faslodex) approved for?
2nd line antiestrogens. Metastatic, post-menopausal ER or PR (+) with disease progression following antiestrogens
What is the MOA of Fulvestrant?
Pure anti-estrogenic activity (breast). Downregulation of ER receptors (100x greater affinity than Tamoxifen)
What is the NCCN recommendation for Anastrozole (Arimidex)
1st line agent (AI) for adjuvant therapy in POST-menopausal women. Use as subsequent therapy for systemic disease