11/10- Breast Cancer Flashcards
Describe the evolution of breast cancer
- Normal breast duct (mutation of gene A) ->
- Proliferative changes (2x risk) (loss of gene B) ->
- Atypical ductal hyperplasia (4x risk) (amplification of gene C) ->
- Ductal carcinoma in situ (10x risk) ->
- Invasive ductal cancer
- Distal metastases
Breast cancer is the #__ cancer and the #__ cancer killer
Breast cancer is the #1 cancer and the #3 cancer killer
(1. lung, 2. colon/rectum)
What is the 5 yr survival for breast cancer?
89.2%
The improvement in prognosis depends on what?
- Early detection
- Adjuvant therapy
- Tamoxifen
- Chemotherapy
What are the breast cancer risk factors?
- High, RR > __
- Moderate, RR __-__
- Little change
High, RR > 4
- Older age
- (Personal) Hx of breast cancer
- Strong FHx, multiple 1’ and 2’ relatives
- Atypical ductal and lobular hyperplasia
Moderate, RR 1.2-2
- Later age at first pregnancy
- Nulliparity
- Menarche under age 12
- Menopause > 55 yo
- Moderate alcohol use (3/wk does not greatly increase risk)
- Prolonged HRT (estrogen only replacement therapy for women without a uterus does not count)
- Obesity
Little change
- Lumpy breasts
- Cigarette smoking
- Oral contraceptives
What are the breast cancer screening guidelines (recently changed!)
- Mammography yearly starting at age 45 and every other year at age 55.
- In Europe: every other year at age 50.
- Individualized screening according to risk is the future
If a woman has had a total hysterectomy and has no breast concerns (dysplasia, etc.), but does have menopausal symptoms, is it okay to give her estrogen-only hormone replacement therapy?
Yes, in terms of breast cancer (there’s no increased risk)
What should be asked/covered in the history of breast problems/cancer?
- Date of onset
- Patient description location
- Prior breast biopsies, cyst aspirations, or problems
- Menstrual status
- Contralateral breast
- Symptoms of metastases
What is the most common metastasis of breast cancer?
Others?
- Bone- ask about bone pain in history
- Pleura
- Liver
Describe the physician’s breast exam (for smaller/medium sized breasts)
- From anterior side
- Circular motion of hand
- Want to roll breast tissue against chest well
- Don’t forget to check axillary lymph nodes
Describe the physician’s breast exam (for larger/heavier breasts)
- Pt standing up with arm raised
- Don’t forget to check axillary lymph nodes
What are diagnostic studies possible for breast cancer?
Mammogram:
- Masses
- Microcalcifications
U/S: NOT for screening; look at specific areas
- Solid vs. cystic
- Mammographically undetected lesions
- Young women under 30 yo
MRI
- Very sensitive, very non-specific
- Only used if known FHx of BRCA genes
What are breast biopsy techniques/methods?
FNA
- Least invasive
- Excellent for suspected cyst
- No histology
Core needle
- Histology, invasive vs. not invasive
- Easier to perform molecular markers
Excision- NO
- AVOID; use only for exceptional problems
What are the common breast cancer types and percentages?
Adenocarcinomas
- Infiltrating ductal (70%)
- Intraductal carcinoma (ductal carcinoma in situ, DCIS) (20%)
- Infiltrating lobular (10%)
What are local treatment methods for breast cancer?
- Mastectomy vs. lumpectomy + radiation
- Three randomized studies showed survival is equal for both, choice is up to the patient
What is the lymph node called where cancer is first found (the one most directly filtering the cancerous area)?
Sentinel lymph node
How is breast cancer staged (with what tests)?
- History, physical
- Chemistry profile, CBC
- CXR, bilateral mammogram
- Other tests not indicated unless:
- Tumor is > 5 cm
- Nodes palpable
- or above tests abnormal
- Bone scan, CT scans, serum tumor markers NOT routinely indicated
- Different from many other cancers, because we don’t really need to stage early breast cancer
Describe the T stage for tumors
T1: primary tumor 2 cm or less
T2: primary tumor 2-5 cm
T3: primary tumor > 5 cm
T4: tumor of any size with extension to the chest wall and skin, including inflammatory carcinoma
Describe the N stage for tumors
N0: No Regional Lymph Nodes
N1: Moveable homolateral lymph nodes (or 1-3 on path)
N2: Homolateral lymph nodes fixed to one an other structures (or 4-9 LN on path)
N3: Homolateral supraclavicular* or infraclavicular lymph nodes (or >9 LN on path) `
Describe the M stage for tumors
M0: no metastasis
M1: distant metastasis
Describe numerical staging
- If M1 at all, it’s Stage IV
- If N3 or T4, it’s Stage III
Describe irradiation of the breast
- Area targeted
- Following what
- Odds of recurrence
- Duration of Rx
External beam
- “Whole” breast external beam radiotherapy follows lumpectomy
- 3/4 of in-breast recurrences occur in the same quadrant
- Incidental tissue treatment
- Requires 6-7 week delivery
Describe the different types of reconstructive surgery
Modified radical mastectomy
- Autologous reconstruction
- TRAM flap (transverse rectus abdominis myocutaneous)
- Latissimus flap
- Gluteal flap
- Expander reconstruction
- Implant
Nipple and areola reconstruction (now there’s even 3D tattoos)
Why is systemic therapy needed for breast cancer?
- Many women with breast cancer will recur if treated with surgery alone
- Breast cancer may recur many years after initial diagnosis
In what (3) settings is systemic therapy used in breast cancer?
- Neoadjuvant: before surgery
- Adjuvant: after surgery
- Metastatic: when incurable
What are systemic therapy options for breast cancer?
- Chemotherapy
- Hormonal therapy (targeting estrogen and progesterone receptors)
- Biologic (targeted) therapy
What are the different types of molecular markers that can be used?
Prognostic markers
- “Inherent” aggressiveness of the cancer
- Factors that determine the natural history of the disease in the absence of adjuvant therapy
Predictive markers
- Factors associated with response or lack of response to a particular therapy
What are some traditional prognostic and predictive markers for breast cancer? New ones?
Traditional:
- Tumor size
- Nodal status
- Histologic grade/type
- Proliferative index
- ER/PR/HER-2
New factors:
- Gene expression profile
- Recurrence score
Describe adjuvant chemotherapy for breast cancer
- Treats what
- Reduces recurrence ____%
- Greater benefit when
- Examples
- Treats micrometastatic disease.
- Reduces recurrence 30-55%.
- Greater benefit in high risk disease, such as large tumor size, involved LN, high grade
- Combination therapy, 4-8 cycles
- Example: AC, TC, AC->Taxane, TAC
Hormonal therapy was the first ____ therapy against ___ breast cancer
Hormonal therapy was the first “targeted” therapy against ER breast cancer
What is the single most effective systemic treatment modality for breast cancer?
Hormonal therapy
- Well tolerated with little toxicity
Describe the outcomes of hormonal therapy when:
- Adjuvant
- Neoadjuvant
- Metastatic
- Adjuvant: decreases risk of recurrence by 50%
- Neoadjuvant: just as effective as chemotherapy but takes longer time
- Metastatic: response rate ~ 50%
When is ovarian suppression used in the treatment of breast cancer?
- Important in pre-menopausal women
- Chemotherapy induced amenorrhea plays a role
What is Tamoxifen?
- Mechanism
- Outcomes
- Active in what pouplation
- First approved hormonal therapy
- Modulates the estrogen receptor
- Five years of tamoxifen decreased recurrence by 45-50% or more
- Active in pre and post menopausal women
- 10 years better than 5
What are aromatase inhibitors?
- Active in what population
- Used when
- Combine with what
- Effective in postmenopausal women with ER+ breast cancer
- Goal is to lower estrogen as much as possible
- Can be used initially or after 2-5 yrs of tamoxifen as adjuvant therapy for early stage disease
- Combined with ovarian suppression for
- Optimal duration unknown
What are the clinically important side effects of adjuvant endocrine therapy?
Tamoxifen
- Endometrial cancer (1%)
- DVT (1%)
- Vaginal dryness (20%)
- Hot flashes (20%)
AIs
- Fractures (2%)
- Myalgias (10-20%)
- Vaginal dryness (20%)
- Hot flashes (20%)
What is the HER-2/neuo oncoprotein?
- Member of what family
- Amplified in ___% of breast cancers
- Effects
- Drug response
- Member of HER (erbB) family
- Amplified in 20-25% of breast cancers
- Decreased DFS and OS
- Tamoxifen resistance
- Anthracycline sensitivity
- Enhances cell proliferation and resistance to apoptosis
Describe the HER pathway activation
- HER1/EGFR
- HER2
- HER3
- HER4
All feed into: PI3K/AKT, Ras/MEK/MAPK (STAT)
- Contribute to TF, CoA, CoR
- Cause proliferation, migration, differentiation, and apoptosis
What is Trastuzumab (Herceptin)?
- Mechanism
- Benefits
Monoclonal antibody against HER-2
- Effective in patients with HER-2/neu positive tumors a single agent (10% response rate) or in combination with chemotherapy (50% vs. 32%)
- Reduces risk of recurrence by 50% in early setting.
Compare the benefit vs. risk of systemic therapy
- Who should get it?
- What treatments should be done for ER+ tumors? HER2+?
Benefit is directly proportional to risk of recurrence
- Most patients with a tumor > 1 cm or any positive nodes should receive systemic therapy.
Treatments:
- Hormone therapy for 5 years for ER-positive tumors.
- Trastuzumab added to chemotherapy for HER2-positive tumors.
What are principles of management of metastatic breast cancer?
- Palliation is the goal
- Sequence therapies.
- When using chemotherapy, single agents
- Hormonal therapy
- Targeted therapy
Who should have hormonal therapy for metastatic breast cancer?
- Patients with estrogen receptor (+) tumors
- Older, postmenopausal patients
- Patients with longer disease-free intervals from mastectomy to recurrence
- Patients with bone, skin, lymph node, pleural, or soft tissue metastasis
- Patients with a previous response to hormonal therapy
What is Everolimus?
mTOR inhibitor
Resistance in breast cancer treatment may arise from what?
Resistance via Cyclin D pathway
When is chemotherapy done for metastatic breast cancer?
- Patients progressing or failing to respond to hormonal therapy
- Patients whose tumors are estrogen receptor negative
- Patients with visceral metastasis: liver, lung abdominal carcinomatosis
- Add anti-HER2 agents for HER2+ patients
What are some HER2 targeted agents? Examples?
- Monoclonal Ab
- Trastuzumab
- Pertuzumab
- TKI
- Lapatinib
- (Neratinib)
- (Afatinib)
- Antibody drug conjugate
- T-DM1 (ado-trastuzmab emtansine)
What is Pertuzumab (Perjeta)?
HER2 targeted agent: monoclonal antibody
What is Trastuzumab emtansine (Kadcyla)?
- Components
- Mechanism
- Trastuzumab (monoclonal antibody): binds to HER2 at subdomain IV to effect anti-HER2 activities.
- MCC* (stable linker): covalently links DM1 to trastuzumab.
- DM1* (cytotoxic maytansinoid) : inhibits tubulin polymerization to induce cell-cycle arrest and cell death.
What lifestyle factors can help in the management of breast cancer?
1. Maintain healthy weight (BMI < 25)
2. Physical activity
- 3-5 hrs of moderate paced walking/wk
- Weight bearing for bones
- Aerobic for CV disease
3. Modest alcohol consumption
- < 3 drinks per wk
- Folic acid 800 ug/day
4. Healthy diet
Describe the relationship between obesity and breast cancer
- Premenopausal
- Postmenopausal
Premen: slight decreased risk due to anovulatory cycles and reduced E and P.
- BMI >= 30 kg/m² = RR 0.6-0.9
Postmen: increased risk due to increased E from aromatization of androgens in fat tissue
- BMI > 30 = RR 1.3
Conclusions
- Breast cancer is a curable cancer.
- Significant improvement have occurred but still can go further
New era of molecular profiling will allow targeted therapy tailored to tumor and patient
