breast ca1

7/30/2019 Breast Ca1

1/25

BREAST CANCER


2/25

EPIDEMIOLOGY

Risk factors

increasing age: rate slows after menopause

early menarche, late menopause , nulliparity

atypical lobular or ductal hyperplasia(benign breast disease)

early exposure to ionizing radiation

long-term postmenopausal estrogen-replacement therapy

alcohol consumption

family history of breast ca.( most important )

- 5 to 10% occur in high-risk families

- familial breast ca. syndrome : breast-ovarian cancer syndLi-Fraumeni synd

Cowden's ds


3/25

BIOLOGY

Genetic abnormalities(1) familial breast ca

BRCA1andBRCA2 germ line mutation

. 50 to 85 % lifetime risk breast ca, ovarian ca, or both

. genetic screening and counseling programs are ongoing

(2) sporadic breast ca

p53, bcl-2, c-myc,c-myb gene abnormality

HER-2/neu


4/25

DIAGNOSTIC APPROACHES

Screening by mammography and physical examination

- early diagnosis

25 to 30 % decrease in mortality over age of 50 yrs

& probably in btw age of 40-50 yrs

American Cancer Society, the National Cancer Institute recommend

1) annual mammography for > 40 yrs2) high-risk families, withBRCA1 orBRCA2 mutant

: at 25 yrs of age

or 5 yrs earlier than earliest age at which breast ca diagnosed

in family member

Standard method for confirming diagnosis

fine-needle aspiration or core needle biopsy


5/25

THERAPY

1. Primary Breast Cancer Local disease without distant spread

curable with local or regional treatment alone

but, most pts have subclinical metastasis

distant metastasis ultimately develop


6/25

1) Local and Regional Treatment

early breast cancer

lumpectomy

(wide excision of tumor with preservation of breast)

with radiotherapy


7/25

2) Axillary Lymph-Node Dissection standard for invasive or large non-invasive tumors (>2.5 cm)

Prognosis information

- recurrence is higher for histologically positive axillary LNs responsible for morbidity associated with surgery

alternative method

: Sentinel-lymph-node mapping


8/25

3) Postop. Adjuvant Therapy

(1) Chemotherapy

(2) Hormone therapy

(3) Radiotherapy

Prognostic factors

Gold Standard

Axillary lymph node status

Tumor size

Histologic subtype, Histologic or nuclear grade

ER and PgR status

Potential

proliferation marker (S-phase fraction, Ki67, TLI )

c-erbB-2(HER-2/neu)


9/25

Axillary LN status and recurrence rate

Positive nodes(No.) 10 year recurrence rate(%)

0 201-3 47

4-6 59

7-12 69

>13 87

Hormone receptor and response to endocrine therapy

Receptor status Response rate(%)

ER -, PR - 10

ER -, PR + 33

ER +, PR - 34

ER +, PR + 74


10/25

Risk categories for pts with node-negative breast ca.

Factors Low Intermediate High

(has all listed factors) (at least one factor)

Tumor size < 1cm 1-2 cm > 2 cm

ER and PgR + - -

Grade Grade I Grade 1-2 Grade 2-3

Age > 35 yrs < 35 yrs


11/25

(1) Adjuvant Systemic Chemotherapy

combination chemotherapy- more effective than single-drug treatment

- effects : marked in < 60 yrs ( esp. premenopausal )

- reduce annual risk of death by 20%

duration of chemotherapy

- usually used combination regimens

: FAC, FEC, CMF ( 6 cycles )

AC ( 4 cycles )


12/25

(2) Adjuvant Hormone Therapy

Tamoxifen- breast ca. is estrogen-dependent

- antiestrogenic activity mediated by competitive inhibition

of estrogen binding to estrogen receptors

- inhibits expression of estrogen-regulated genes including

growth factors and angiogenic factors secreted by tumor

reduce recur & death in all age group

- when to estrogen-receptor-positive tumor

- when for about 5 yrs, rather than 1 to 3 yrs

( for more than 5 yrs is no more effective than for 5 yrs )


13/25

Adjuvant therapy fornode-negative breast ca.

(1998 International Consensus)

Pt group Low risk Intermediate risk High risk

Premenopausal, ER or PgR + None or TMF TMF + CTX CTX + TMF

ER and PgR - NA NA CTX

Postmenopausal, ER or PgR + None or TMF TMF + CTX TMF + CTX

ER and PgR - NA NA CTX

Elderly None or TMF TMF TMF

ER: estrogen receptor, PgR: progesteron receptor

TMF : tamoxifen, CTX : chemotherapy, NA : not applicapable


14/25

Adjuvant therapy fornode-positive breast ca.

(1998 InternationalConsensus)

Pt group Minimal/low risk

Premenopausal, ER or PgR + CTX + TMF

ER and PgR - CTX

Postmenopausal, ER or PgR + TMF + CTX

ER and PgR - CTX

Elderly TMF

ER: estrogen receptor, PgR: progesteron receptor

TMF : tamoxifen, CTX : chemotherapy


15/25

(3) Adjuvant Radiotherapy (RT)

Postmastectomy RT

- reduces local recur by 50-75%

but this reduction was not accompanied by increased survival

so, postop. RT indication

only for high risk local recur. pts

- large tumors > 5 cm

- invading the skin of the breast or chest wall

- many (> 4 ) positive axillary LNs


16/25


17/25

4) Preoperative Chemotherapy

- large operable tumor

- 90% of tumor decrease in size by more than 50%

- lumpectomy possible

- survival benefit : no apparent advantage

as compared with postop. chemotherapy

5) Dose-Intensive and High-Dose Chemotherapy Regimens

- ongoing randomized trial should help to determine the efficacy


18/25

2. Locally Advanced and Inflammatory Breast Ca.1) Stage III breast ca.

tumor > 5 cm in diameter

any size with invasion of skin of breast or chest wall

any tumors with fixed or matted axillary LNs

2) Inflammatory breast ca.

- should treat withpreoperative chemotherapy or hormonal therapy

- excellent local control achieved in 80 to 90% of pts

and 30% pts remain free of cancer after 10 yrs


19/25

3. Metastatic Breast Cancer

clinical course is variable- large variation in growth rate and responsiveness

to systemic therapy

main goals of treatment- optimal palliation and prolongation of life

therapeutic strategy on basis of

age, disease-free interval, hormone-receptor status,

and extent of disease


20/25

1) Hormonal intervention- 20 to 35% response to initial hormonal therapy

- 10 to 20% to second-line

- 15 to 30% to another

Hormonal Therapies for Metastatic Breast Ca.

Order of Tx. Premenopausal Postmenopausal

First line Antiestrogens or ovarian ablation Antiestrogens(chemical, surgical or postRT)

Second line Ovarian ablation after antiestrogens Aromatase inhibitors*

; antiestrgens after ovarian ablation

Third Liline Progestins ProgestinsForth line Androgens Androgens or estrogens

* Aromatase inhibitor: Formestane, Anastrozole(Arimidex), Letrozole(Femara)

Metastatic Breast Cancer


21/25

2) Chemotherapy

- refractory to hormonal therapy

40 to 60% response to CMF

- anthracycline-containing combination superior to CMF

50 to 80% response to FAC

- new drugs

vinorelbine( third-generation vinca alkaloid )

taxanes (paclitaxel and docetaxel)

* Combinations of taxanes and anthracyclines

responses in 40 to 94%

complete remissions in 12 to 41%



22/25

Bone

- most common site of metastasis

cause of substantial morbidity, complication

* Bisphosphonate (pamidronate and clodronate)add to chemotherapy or homonal therapy

- reduce pain and complication

- prolong survival free of bone-related event



23/25

3) High-Dose Chemotherapy

I. single cycle of high-dose combination of cytotoxic drug(usually alkylating agent)

bone marrow damage is earliest limiting toxic effect

- eliminated by reinfusing autologous hematopoietic stem cell

II. 2 to 4 cycles of cytotoxic-drug combination

at dose higher than usual but not ablate bone marrow

higher complete remission (40 to 60%)

15 to 25% free of cancer for 3 to 5 yrs

Metastatic Breast Canc


24/25

CHEMOPREVENTION

administration of adj. tamoxifen for 5yrs after primary Tx.

- reduce incidence of contralat. breast ca. by 47%

- endometrial ca. in twice

- increase in thromboembolic event

occured predominantly in older than 50 yrs

* overall beneficial effect of tamoxifen

outweighed adverse effect


25/25

NOVEL THERAPIES

HER-2/neu oncogene overexpressed in 20 to 30%

- more aggressive

- more resistant to chemotherapy

13% of metastatic breast ca with HER-2/neu

- response to monoclonal antibody againstextracellular domain of HER-2/neu oncoprotein

chemotherapy combined with anti HER-2/neu antibody- increase response rate & prolongation of survival

breast ca1

Documents