IM 3B: ONCOLOGY EPIDEMIOLOGY:

BREAST CANCER Breast cancer is a hormone-dependent disease

SOURCE: 2017 PPT
February 2017
BREAST CANCER
Malignant proliferation of cancer cells lining the ducts or lobules of the breast
Epithelial malignancies of the breast are the most common cause of cancer in the
women (excluding skin cancer) 1/3 in the US
Improve treatment and earlier detection resulted to decrease mortality rate from
breast cancer in the US
Is a clonal disease.
- a single transformed cell- the product of a series of somatic (acquired) or
germline mutations is eventually able to express full malignant potential.
GENETICS
1. Li-Fraumeni Syndrome is characterized by inherited mutations in the p53 tumor-
suppressor gene, which lead to an increased incidence of breast cancer.
2. Inherited mutations in PTEN
3. BRCA 1- another TSG has been identified at the chromosomal locus 17q2 1
- this gene encodes a zinc finger protein and the protein product functions as a
transcription factor and is involved in a gene repair
- Women who inherit a mutated allele of this gene from either parent have at least
60-80% lifetime chance of developing breast cancer and about 33% chance of
developing ovarian cancer
- Ashkenazi Jewish descent- high likelihood of a specific founder BRCA 1mutation
(substitution of adenine from guanine at position 185)
4. BRCA2- localized to chromosome 13q12, is also associated with an increased
incidence of breast cancer in men and women
*Patients with strong family histories should be referred to genetic screening
programs
*These genes also have an important role in sporadic breast cancer
The female-to-male ratio is about 150:1
The three dates in a womans life that have a major impact on breast cancer
incidence are:
- Age at menarche. Women who experience menarche at age 16 years have only
50-60% of the breast cancer risk of a woman having menarche at age 12 years;
the lower risks persists throughout life
- Age at menopause occurring over 10 years before the median age of
menopause (52 years) whether natural or surgically induced reduces lifetime
breast cancer risks by about 35%
- Age at first full time pregnancy. Women who have a first full term pregnancy by
age 18 have a 30-40% lower risk of breast cancer compared with nulliparous
women.
Duration of maternal nursing correlates with substancial risk reduction independent
of either parity or age at first full-term pregnancy
EVALUATION OF BREAST MASS:
Examination of the breast is an essential part of physical examination
- Women should be trained in Breast Self Examination (BSE)
- Although breast cancer in men is unusual, unilateral lesions should be evaluated in
the same manner as in women
- All breast cancer is diagnosed by biopsy of a nodule detected either on a
mammogram or by palpation.
ALGORITHM FOR BREAST MASS ALGORITHM FOR CYST
PALPATION MANAGEMENT:

erbB2 (HER/2 neu)

- A dominant oncogene plays a role in about a quarter of human breast cancer cases
- Member of the epidermal growth factor receptor superfamily
- Overexpressed in breast cancers due to gene amplification
- This overexpression can contribute to transformation of human breast epithelium
and is the target of effective sysytemic therapy in adjuvant and metastatic disease
settings
- Trastuzumab, Lapatinib, Pertuzumab, Ado-trastuzumab, emstatine

IM 3B: Oncology - Breast cancer , Elka Bungay 1 of 4

 ALGORITHM FOR DIAGNOSIS: MAMMOGRAPHY ALGORITHM

BREAST CANCER SUBTYPES:

STAGING: 1. Luminal A
- Express CK 8 and 18
- Have the highest levels of estrogen receptor expression
- Tend to be low grade
- Are most likely to respond to endocrine therapy
- Have a favorable prognosis
- Tend to be less responsive to chemotherapy

2. Luminal B
- Tumor cells are also of luminal epithelial origin
- gene expression pattern distinct from Luminal A
- Prognosis is somewhat worse than luminal A

3. Normal breast-like
- Gene expression profile of nonmalignant normal breast epithelium
- Prognosis is similar to the luminal B group
- Somewhat controversial and may represent contamination of the sample by
normal mammary epithelium

4. HER2 amplified
- Have amplification of HER2 gene on chromosome 17q and frequently exhibit
coamplification and overexpression of other genes adjacent to HER2
- Historically, poor clinical prognosis
- Prognosis improve the advent of trastuzumab and other targeted therapies

5. Basal
- Triple negative breast cancer
- Characterized by markers of basal/myoepithelial cells
- Tend to be high grade and express cytokeratins 5/6 and 17 as well as vimentin
p63 , CD 10, a-smooth muscle actin and epidermal growth factor receptor
(EGFR)
- Patients with BRCA mutations, They also have stem cell characteristics

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PROGNOSTIC VARIABLES: PREMENOPAUSAL TREATMENT:
Tumor stage tumor size, LN Histologic classification- nuclear Multi-drug therapy
involvement, LVSI grade Anti-hormone therapy improves in survival in premenopausal patients who are ER
ER/PR status Molecular changes- her 2/neu positive
Tumor growth rate- Ki-67 positive
- should be added following completion of chemotherapy
Prophylactic surgical or medically induced castration may also be associated with a
substantial survival benefit
TREATMENT:
A. SURGERY POST-MENOPAUSAL TREATMENT:
Modified Radical Mastectomy Chemotherapy VS Endocrine therapy
Breast Conserving Surgery Adjuvant endocrine therapy (aromatase inhibitors and tamoxifen =) improves
- not generally for tumors >5cm, tumors with extensive intraductal disease
survival regardless of axillary lymoh node status
involving multiple quadrants of the breasts, women with history collagen- - If (+) lymph node involvement, the improvement in survival is modest-
vascular disease, women without motivation for BCS or do not have convenient chemotherapy given to patients with no medical contraindications and who have
access to radiation therapy more than one positive lymph node
Hormone therapy may be used alone for patients with more favorable prognosis
B. RADIATION (based on analysis such as the Oncotype DX methodology)
Adjuvant post lumpectomy decrease recurrence
Adjuvant post MRM in high risk patients- T2, (+) margins, (+) lymph nodes- improve - Oncotype DX analyzes the expression of a panel of 21 genes within a tumor to
survival and decrease local recurrence determine a recurrence score.

C. CHEMOTHERAPY
Neoadjuvant- chemotx before definitive surgery and RT
- Downstage tumor for BCS but OS not increased
- OS increased in those who achieved Pcr
Adjuvant- improve OS
- Use taxanes, Paclitaxel, Docetaxel; anthracyclines, Doxorubicins, Epirubicin;
Alkylating agent Cyclophosphamide
- Trastuzumab for Her2 (+) disease given for 1 year
Dose dense in adjuvant setting
- Administration of the same drug combinations at the same dose but at more
frequent intervals
- Even more effective

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 METASTATIC DISEASE/ RECURRENT DISEASE: FOLLOW UP:
Should rarely be made without a confirmatory biopsy
Changes in hormone receptor status can occur and alter treatment decisions
Goal: PALLIATIVE
If localized- local treatment (RT, Surgery)
Hormone receptor (+) endocrine therapy
Poor response to endocrine therapy
- Short disease free intervals
- Rapidly progressive visceral disease
- Lymphangitic pulmonary disease
- Intracranial disease

NON-INVASIVE BREAST CANCER

DCIS- proliferation of cytologically malignant breast epithelial cells within the ducts
Treatment- Mastectomy, Lumpectomy with RT, Tamoxifen
Lobular Neoplasia- proliferation of cytologically malignant cells within the lobules
Treatment: SERM, AI

MALE BREAST CANCER

Presents as unilateral lump
- In-patients >40 y/o BIOPSY
Prognosis identical to female breast cancer
Treatment: mastectomy with ALND or SLNB
60% responds to endocrine therapy
- 90% are ER positive
Adjuvant chemo and RT if not nedically contraindicated

Early detection SAVES LIVES!

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