Reproduction System- Breast Cancer By Nazar

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Reproduction System- Breast Cancer by Nazar

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Reproduction System- Breast Cancer by Nazar

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Breast cancer is the leading cause of non-skin cancer in women

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truth.

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5-year survival for localized disease

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5-year survival for localized disease (no lymph node or distant mets) is 97%

More feared than Heart Disease which is much more common

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Risk Factors for Breast Cancer

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Early menarche (before age 12)
Late menopause (after age 55)
No pregnancies / 1st pregnancy after 30 yo
Hormone replacement therapy
Especially in use with EtOH
Oral contraceptives NOT found to be risk
NEJM, June 2002
Still somewhat controversial; may be overall very slight risk

*uninterrupted menstrual cycles increases the risk of BC
ESTROGEN ESTROGEN ESTROGEN!

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Most cases of BC happen with family history, right?

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80% occur in women WITHOUT family history!!!

high alcohol intake, low vitamin E, beta carotene, vit. D also are risk factors.

smoking decreases survival in BC patients (not a CAUSE, but it doesn't help)

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Genetic Risk Factors

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Found in < 10-20% of cases

Mutations in genes BRCA1 and BRCA2
-For BRCA1, 50% risk by age 70
-For BRCA2, 37% risk by age 70

Other defective genes: BRCA3, p53-suppressor, NOEY2
-HER2/neu proto-oncogene: aggressive subtype
Rare association with ataxia- telangiectasia dx ( these are more susceptible to radiation harm, eg. mammography)

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The Gail Model Risk Assessment Tool

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Calculate lifetime and 5 yr risk of developing BC compared to the average population. Simplistic so doesn’t tell whole story, but a good screening tool.

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How often do you do self exams, clinical exams, mammomography?

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Breast Self Examination - Monthly after the age of 20 (not supported by EBM)

Clinical Breast Examination - Every 3 years from 20 - 39

Mammography - Yearly after the age of 40 (ACS, ACR, AMA, NCI all
recommend)

NOT A HIGHER SURVIVAL RATE IF YOU DO YOUR OWN BREAST EXAMS bc if it’s big enough to palpate, it’s already too big.

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Mammography: Earlier screening for higher risk women

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Family hx of bilateral or premenopausal breast cancer (10yrs earlier than age at dx or age 25, whichever older)

Hx of high dose mantle radiation (eg Hodgkins’s lymphoma); start 8 years after treatment

Sensitivity of Mammo:
Overall sensitivity of 75-89%
-Less sensitive with dense fibroglandular tissue

In true screening setting, approx 10% women will be recalled for additional imaging
-1% will require biopsy; 25 – 40% will be + for cancer
-Vast majority of recalled pts will need only further imaging (not because there’s cancer)

use ultrasound in conjunction with mammogram for screening.

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Most common breast mass and characteristics

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benign cyst.

-In the setting of the fibrocystic process
-Cyclic hormonal stimulation
-Round to elliptical, freely mobile
-No dimpling or retraction
-May be tender premenstrual

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Fibroadenoma

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Benign, solid mass, usually round
Well demarcated, freely mobile
Usually nontender
*Rubbery or firm
No retraction or fixation

STAND OUT FROM SURROUDING TISSUE. THEY DON’T BLEND IN LIKE MALIGNANCIES

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Classic Physical Signs of Breast Cancer

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-Irregular in contour
-Firm to hard consistency
-Not well delineated from surrounding tissue
-Nontender
-Fixation- chest wall is stuck
-Retraction
-Dimpling- orange peel
*Some or all of these may be present and their absence does not exclude cancer!

inflammatory- will see orange peel (fibrosis?)
most in the upper out quadrant, 17% under nipple.

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What is the earliest stage of breast cancer indicated with? How curable is this?

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Ductal Carcinoma in situ (DCIS):
--earliest stage of breast cancer; confined to ducts
--nearly 100% curable

Infiltrating (invasive) ductal carcinoma (IDC)
--80% of all breast cancers
--begins in duct, invades and spreads

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Lobular carcinoma in situ (LCIS) vs Infiltrating (invasive) lobular carcinoma (ILC)

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Lobular Carcinoma in situ (LCIS)
-not a true cancer but increases risk; usually no treatment, so just monitor for it

Infiltrating (invasive) Lobular Carcinoma (ILC)
--10-15% of all breast cancers
--be - gins in lobules and spreads

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When do you do a biopsy?

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either a palpable mass and/oran abnormal mammogram brings the patient to biopsy.

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What are possible causes for skin retraction or dimpling?

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Skin retraction or dimpling causes include
1. Fat necrosis
2. Previous breast trauma/surgery/Bx
3. Mondor’s disease (thrombophlebitis of the breast or penis)
4. Breast cancer

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stereotactic bx

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for the nonpalpable lesion.done under mamographic guidance; important. Takes a week to get an answer. That’s a long time.

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Pre-treatment Work-up for biopsy

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Clinical Staging: to evaluate the extent of disease
T: Size of the primary tumor
N: Involvement of lymph nodes
M: Presence of distant spread metastasis)
TNM system to define treatment & prognosis: Stages 0 (TisN0M0) thru Stage IV (anyT,anyN,M1)

T1: <2cm, T2: 2>x<5, T3: >5cm, T4: tumor extends to chest wall/skin

Mx: cannot assess, Mo: no distant mets, M1- distant mets (including ipsilateral supraclavicular nodes)

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The presence of what is a critically important prognostic variable and how this can be done

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The presence of involved lymph nodes is a critically important prognostic variable.

This can be done by either:
Sentinel lymph node dissection
vs
Axillary lymph node dissection

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Where does a majority of lymphatic drainage go?

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Lymphatic drainage is to the axilla (armpit). This accounts for approximately 75% of the lymphatic drainage.

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These are associated with a poor prognosis:

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Large primary tumor size
Negative estrogen and progesterone receptors
High histologic grade
High proliferative rate (S-phase fraction)
Certain histologic subtypes
Over-expression of certain oncogenes
-HER- 2/neu; Er-B-2, EGF, myc

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Pros/Cons of Mastectomy

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Benefit = one surgery done as inpatient, with usual recovery period of 1 week or so. Usually no radiation is needed, although that is changing today

Disadvantages = long recovery in some women. Sexual implications of loss of breast. Cosmetically less acceptable for some

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Pros/Cons of Lumpectomy

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Benefits = breast is preserved. Quicker recovery period with the more limited surgery.Cosmesis is generally good

Disadvantages = all women with this have to get radiation which is inconvenient(6 to 7 weeks daily). Radiation may be far away.

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Contraindications to Breast Conservation Therapy

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Pregnancy
Skin connective tissue disorder(RA,SLE)
Previous XRT to the breast
Cosmesis will be impaired(breast too small or too large)
Multicentric disease
Previous XRT(eg Hodgkins-mantle) is relative contraindication

Does it affect survival?
-Absolutely NOT
--Women live the same regardless of which surgery they get(lumpectomy or mastectomy).
-The amount of surgery only determines the likelihood of a local recurrence.

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Radiation Therapy.. how long is therapy

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Megavoltage radiation
Cosmesis excellent
Daily therapy for 6 to 7 weeks
It is used in the setting of breast preservation in all women
In some mastectomy patients it is also required.
It can be given before or after surgery, but usually is given after surgery

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When do you give chemotherapy? Name some drugs, and side effects.

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Chemotherapy given if the risk exists that the cancer has spread-this is determined by the size of the tumor, the grade, the presence or absence of nodes, age, and other factors.

Agents typically given are CMF, CAF, FEC, AC, Taxotere

Cyclophosphamide, methotrexate, 5-FU (CMF) has been gold standard; Xeloda , orally taken 5-FU

Taxol, Taxotere for advanced disease

Side effects common: fatigue, nausea, diarrhea, hair loss, weight loss, depression, suppression of the body’s immune system (all temporary)

Complications: infection, bleeding, secondary cancers (eg. leukemia)

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Selective Estrogen-Receptor Modulators (SERMs) as hormone therapy. what is the prototype? what is a serious risk of using these?

Compare to reloxifene.

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Tamoxifen (Nolvadex) is prototype:
-Typically administer for five years after surgery
-It is not a primary/sole treatment
-Also has use prophylactically to prevent first and second breast cancers
-May use both pre- and post- menopause
-Serious risk of endometrial cancer, thrombotic events (do not use if h/o PE,DVT)

Raloxifene as effective in prophylaxis of invasive breast cancer
Fewer uterine side effects with Raloxifene
Bone benefits

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Aromatase Inhibitors.
How do they work?
Who is it for?
Name the drugs.

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Prevent the production of estradiol by blocking enzyme aromatase

For post-menopausal women with estrogen receptor positive breast cancers

Four to know:
Arimedex (anastrazole)
Aromasin (exemestane)
Femara (letrozole)
Fadozole (third generation)

Given as first line post-treatment prophylaxis OR after SERM treatment

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Biologically Targeted Therapies... what has the worse prognosis?

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Humanized HER-2 targeted antibody, trastuzmab, HERCEPTIN

HER-2 expressing tumors have worse prognosis (know this!)

Protocols often include weekly treatments for one year