275. Breast Cancer

Question 1

Breast Cancer Epi

• basic epi
• screening
• explain mortality trend
• overall risk of developing breast cancer

Answer 1

Most commonly dx cancer worldwide, most common female cancer, 2nd most common cause of cancer death in women
Screening: mammogram
Mortality decreasing since 1970 due to improved screening and improved adjuvant therapy
1 in 8 overall lifetime risk (but HIGH survival, unless distant mets…)

Question 2

BCa: RF

- What are the four key categories of risk factors and specific types of each

Answer 2

1. General: increasing age: median 62; female gender, ionizing radiation, lifestyle (obesity, decreased physical activity, alcohol, smoking)
2. Hormonal: increased E exposure (early menarche, late mp, late first pregnancy, nulliparity), HRT, OCPs, increased breast density
3. Genetics: majority are BRCA1/2, less common hereditary syndromes (li fraumeni - TP53, Cowden Syndrome - PTEN - hamaratoma, papilloma, macrocephaly)
4. Pathological: Proliferative breast lesions - without atypia (UDH), atypical hyperplasia (ADH, ALH, need for excision), in situ (DCIS = premalignant; LCIS = not premalignant but need excision still), hx of invasive BCa

Question 3

What are the 4 prevention strategies to reduce breast cancer risk?

Answer 3

1. Bilateral prophylactic mastectomy (decrease risk by 90%)
2. Enhanced screening (MRI)
3. Chemoprevention: pre-mp = tamoxifen; post-mp = tamoxifen, raloxifene, aromatase inhibitor
4. Lifestyle modifications: less alcohol, exercise, weight control, smoking cessation

Question 4

BCa Dx/Screening

• how is BCa dx and how does each work? (3)
• what is the benefit of screening? who benefits most? when to start?
• what are three key markers in BCa molecular profile, what are two measures of aggressiveness?

Answer 4

1. Mammogram: low dose Xray to visualize internal breast structure - now digital, uses digital tomosynthesis to make 3D mammogram
2. US - further eval abnormalities on mammogram (adjunct, esp for dense breasts)
3. MRI - for women with higher than average risk, more sens but less spec (>20% False positives)

Screening: decrease mortality, early detection, higher cure
Increased benefits for middle age = due to more incidence of cancer and longer life expectancy

Start: varies, but usually start at 40yo (30 if high risk, or MRIs at 25 if high risk)

1. ER 2. PR 3. Her2
2. Grade
3. Ki-67

Question 5

What is the most common and second most common types of breast cancer?
What subtypes have less favorable prognosis? more favorable prognosis?

What is the most common molecular subtype of breast cancer? How to tx? Prognosis? two classes of this?

Answer 5

Most common: IDC (70-80%)
2nd most common: ILC (higher risk bilateral disease, multicentric disease, usually E responsive with favorable prognosis)

Less favorable: Metaplastic
More favorable: Mucinous, Tubular, ~Medullary

Most common: Hormone Receptor + (ER/PR+), tx with anti-E tx (tamoxifen, aromatase-i), favorable prognosis
Luminal A: higher ER, low Ki67, better prognosis
Luminal B: lower ER, higher Ki67, worse prognosis

Question 6

What is the prognosis, tx of Her2+ breast cancer?

What is an aggressive, inferior prognosis breast cancer with no targeted tx?

When is breast cancer staged? What are the stages?

Answer 6

Her2: most aggressive with poorer outcomes, but now have good tx! (Trastuzumab)

Triple Negative Breast Cancer

Stage 1 & 2 > only if sx
Stage 3 > irrespective of sx due to more mets

T1 <2cm
T2 2-5cm
T3 >5cm
T4 distant mets

Question 7

Treatment of Early Stage Breast Cancer

• how many patients have early stage breast cancer?
• what is the tx? what is the goal of tx?
• how do you evaluate LNs?
• what are the three types of systemic therapy? SE of each

Answer 7

Majority of pts dx with early stage (confined to breast +/- LNs)
Tx: Combination of surgery (Move away from radical mastectomy, now just mastectomy - modified/simple, skin sparing, or lumpectomy - partial mastectomy that requires radiation), radiation (elicit dsDNA breaks, increases risk of edema), systemic medical therapy
Goal: cure or prevention of recurrence and metastatic disease
Eval LN: Sentinel LN biopsy/dissection - only do axillary LN dissection if clinically involved

1. Endocrine Therapy: Tamoxifen (pre-mp women - SERM - antagonist breast, agonist bone/uterus), Aromatase-i (for post-mp women - inhibits E synthesis), Ovarian suppression - adjunct for young women
   SE: E deprivation (hot flashes, decreased libido, vaginal dryness), uterine cancer, thromboembolic disease (Tamoxifen), AI causes arthralgias, less BMD
2. Adjuvant/Neoadjuvant Chemotx
   - for triple + cancer and node+ cancer
   - no difference pre or post op
   - Anthracyclines (cardiotoxicity) +/- taxanes (neurotoxicity, pulm toxicity, hepatotoxicity, MSK myalgia/arthralgia)
   - SE: alopecia, myelosuppression, fatigue, GI, infertility, secondary malignancy
3. Targeted: Anti-HER2 tx: Trastuzumab (anti-Her2, Her4, cardiotoxicity), Pertuzumab (anti-Her2, Her3, synergy with trastuzumab, diarrhea)

Question 8

Treatment approach to metastatic Breast Cancer

• what stage is metastatic? most common sites of mets?
• goals of tx (3)
• types of tx utilized

Answer 8

STAGE IV disease
Sites: bone, liver, lungs, CNS
NOT Curable
Goals: 1. disease control, 2. QoL (use less aggressive tx when possible), 3. Prolongation of life
Tx: Palliative radiation, no surgery
Meds: Targeted therapy when appropriate, E therapy (tamoxifen, AIs), Ovarian suppression (pre-mp women), Combinations with newer CK4/6, mTOR, PIK3CA inhibitors, Her-2 directed tx, 
Triple- Disease: Chemotx
- USE CLINICAL TRIALS