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a_GYNGU > 11/10- Breast Cancer > Flashcards

11/10- Breast Cancer Flashcards

1
Q

Describe the evolution of breast cancer

A
  • 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
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2
Q

Breast cancer is the #__ cancer and the #__ cancer killer

A

Breast cancer is the #1 cancer and the #3 cancer killer

(1. lung, 2. colon/rectum)

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3
Q

What is the 5 yr survival for breast cancer?

A

89.2%

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4
Q

The improvement in prognosis depends on what?

A
  • Early detection
  • Adjuvant therapy
  • Tamoxifen
  • Chemotherapy
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5
Q

What are the breast cancer risk factors?

  • High, RR > __
  • Moderate, RR __-__
  • Little change
A

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
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6
Q

What are the breast cancer screening guidelines (recently changed!)

A
  • 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
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7
Q

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?

A

Yes, in terms of breast cancer (there’s no increased risk)

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8
Q

What should be asked/covered in the history of breast problems/cancer?

A
  • Date of onset
  • Patient description location
  • Prior breast biopsies, cyst aspirations, or problems
  • Menstrual status
  • Contralateral breast
  • Symptoms of metastases
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9
Q

What is the most common metastasis of breast cancer?

Others?

A
  1. Bone- ask about bone pain in history
    - Pleura
    - Liver
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10
Q

Describe the physician’s breast exam (for smaller/medium sized breasts)

A
  • From anterior side
  • Circular motion of hand
  • Want to roll breast tissue against chest well
  • Don’t forget to check axillary lymph nodes
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11
Q

Describe the physician’s breast exam (for larger/heavier breasts)

A
  • Pt standing up with arm raised
  • Don’t forget to check axillary lymph nodes
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12
Q

What are diagnostic studies possible for breast cancer?

A

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
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13
Q

What are breast biopsy techniques/methods?

A

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
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14
Q

What are the common breast cancer types and percentages?

A

Adenocarcinomas

  1. Infiltrating ductal (70%)
  2. Intraductal carcinoma (ductal carcinoma in situ, DCIS) (20%)
  3. Infiltrating lobular (10%)
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15
Q

What are local treatment methods for breast cancer?

A
  • Mastectomy vs. lumpectomy + radiation
  • Three randomized studies showed survival is equal for both, choice is up to the patient
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16
Q

What is the lymph node called where cancer is first found (the one most directly filtering the cancerous area)?

A

Sentinel lymph node

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17
Q

How is breast cancer staged (with what tests)?

A
  • 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
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18
Q

Describe the T stage for tumors

A

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

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19
Q

Describe the N stage for tumors

A

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) `

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20
Q

Describe the M stage for tumors

A

M0: no metastasis

M1: distant metastasis

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21
Q

Describe numerical staging

A
  • If M1 at all, it’s Stage IV
  • If N3 or T4, it’s Stage III
22
Q

Describe irradiation of the breast

  • Area targeted
  • Following what
  • Odds of recurrence
  • Duration of Rx
A

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
23
Q

Describe the different types of reconstructive surgery

A

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)

24
Q

Why is systemic therapy needed for breast cancer?

A
  • Many women with breast cancer will recur if treated with surgery alone
  • Breast cancer may recur many years after initial diagnosis
25
Q

In what (3) settings is systemic therapy used in breast cancer?

A
  1. Neoadjuvant: before surgery
  2. Adjuvant: after surgery
  3. Metastatic: when incurable
26
Q

What are systemic therapy options for breast cancer?

A
  1. Chemotherapy
  2. Hormonal therapy (targeting estrogen and progesterone receptors)
  3. Biologic (targeted) therapy
27
Q

What are the different types of molecular markers that can be used?

A

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
28
Q

What are some traditional prognostic and predictive markers for breast cancer? New ones?

A

Traditional:

  • Tumor size
  • Nodal status
  • Histologic grade/type
  • Proliferative index
  • ER/PR/HER-2

New factors:

  • Gene expression profile
  • Recurrence score
29
Q

Describe adjuvant chemotherapy for breast cancer

  • Treats what
  • Reduces recurrence ____%
  • Greater benefit when
  • Examples
A
  • 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
30
Q

Hormonal therapy was the first ____ therapy against ___ breast cancer

A

Hormonal therapy was the first “targeted” therapy against ER breast cancer

31
Q

What is the single most effective systemic treatment modality for breast cancer?

A

Hormonal therapy

  • Well tolerated with little toxicity
32
Q

Describe the outcomes of hormonal therapy when:

  • Adjuvant
  • Neoadjuvant
  • Metastatic
A
  • Adjuvant: decreases risk of recurrence by 50%
  • Neoadjuvant: just as effective as chemotherapy but takes longer time
  • Metastatic: response rate ~ 50%
33
Q

When is ovarian suppression used in the treatment of breast cancer?

A
  • Important in pre-menopausal women
  • Chemotherapy induced amenorrhea plays a role
34
Q

What is Tamoxifen?

  • Mechanism
  • Outcomes
  • Active in what pouplation
A
  • 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
35
Q

What are aromatase inhibitors?

  • Active in what population
  • Used when
  • Combine with what
A
  • 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
36
Q

What are the clinically important side effects of adjuvant endocrine therapy?

A

Tamoxifen

  • Endometrial cancer (1%)
  • DVT (1%)
  • Vaginal dryness (20%)
  • Hot flashes (20%)

AIs

  • Fractures (2%)
  • Myalgias (10-20%)
  • Vaginal dryness (20%)
  • Hot flashes (20%)
37
Q

What is the HER-2/neuo oncoprotein?

  • Member of what family
  • Amplified in ___% of breast cancers
  • Effects
  • Drug response
A
  • 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
38
Q

Describe the HER pathway activation

A
  • 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
39
Q

What is Trastuzumab (Herceptin)?

  • Mechanism
  • Benefits
A

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.
40
Q

Compare the benefit vs. risk of systemic therapy

  • Who should get it?
  • What treatments should be done for ER+ tumors? HER2+?
A

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.
41
Q

What are principles of management of metastatic breast cancer?

A
  • Palliation is the goal
  • Sequence therapies.
  • When using chemotherapy, single agents
  • Hormonal therapy
  • Targeted therapy
42
Q

Who should have hormonal therapy for metastatic breast cancer?

A
  • 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
43
Q

What is Everolimus?

A

mTOR inhibitor

44
Q

Resistance in breast cancer treatment may arise from what?

A

Resistance via Cyclin D pathway

45
Q

When is chemotherapy done for metastatic breast cancer?

A
  • 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
46
Q

What are some HER2 targeted agents? Examples?

A

- Monoclonal Ab

  • Trastuzumab
  • Pertuzumab

- TKI

  • Lapatinib
  • (Neratinib)
  • (Afatinib)

- Antibody drug conjugate

  • T-DM1 (ado-trastuzmab emtansine)
47
Q

What is Pertuzumab (Perjeta)?

A

HER2 targeted agent: monoclonal antibody

48
Q

What is Trastuzumab emtansine (Kadcyla)?

  • Components
  • Mechanism
A
  • 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.
49
Q

What lifestyle factors can help in the management of breast cancer?

A

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

50
Q

Describe the relationship between obesity and breast cancer

  • Premenopausal
  • Postmenopausal
A

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
51
Q

Conclusions

A
  • 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

a_GYNGU (17 decks)

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