Malignant Breast disorders - PowerPoint Presentation

Slide1

Malignant Breast disorders

Slide2

RISK FACTORS FOR BREAST CANCER

Family

Hx

.: first-

and second-degree relatives with breast cancer and their age at diagnosis

.

Slide3

RISK FACTORS FOR BREAST

CANCER

(

cont.)

Hormonal

Risk Factors

↑ exposure to estrogen → ↑ risk for breast

cancer:

-factors

that increase the number of menstrual cycles, such as early menarche,

nulliparity

, and late menopause, are associated with increased risk

.

-obesity is associated increased breast cancer risk. Because the major source of estrogen in postmenopausal women is the conversion of androstenedione to

estrone

by adipose tissue, obesity is associated with a long-term increase in estrogen exposure

.

-so older age at first live birth is associated with an increased risk of breast cancer

whereas ↓ exposure → thought to be protective.

-Moderate

levels of exercise and a longer lactation period, factors that decrease the total number of menstrual cycles, are protective.

-The

terminal differentiation of breast epithelium associated with a full-term pregnancy is also protective,

so older age at first live birth is associated with an increased risk of breast cancer.

Slide4

RISK FACTORS FOR BREAST

CANCER (cont.)

Nonhormonal

Risk Factors

radiation

exposure.

Survivors

of the atomic bomb blasts in Japan during World War II have a very high incidence of breast cancer,

radiation

exposure during adolescence, a period of active

breast

development, magnifies the deleterious effect.

alcohol

consumption

increases the

risk of breast

cancer.

Alcohol consumption is known to increase serum levels of estradiol.

long-term consumption of foods with a high fat

contributes

to an increased risk of

breast cancer

by increasing serum estrogen levels

.

Slide5

Risk Management

e.g.

when

to use postmenopausal hormone

replacement therapy.

at what age to begin mammography screening

or incorporate

magnetic resonance imaging (MRI)

screening.

When to use tamoxifen to prevent breast

cancer.

when to

perform prophylactic

mastectomy to prevent breast cancer

.

Breast Cancer Screening

.

When Risk-reducing

salpingo

-oophorectomy

When Chemoprevention.

Slide6

EPIDEMIOLOGY AND NATURAL

HISTORY OF BREAST CANCER

Epidemiology

Breast cancer is the most common site-specific cancer in

women and

is the leading cause of death from cancer for women

aged 20

to 59 years

.

The increase in breast cancer incidence occurred

primarily in

women ≥55

years.

There is a 10-fold variation in breast cancer

incidence among

different countries worldwide.

Slide7

Natural

History

Bloom

and colleagues described the natural history of

breast cancer

based on the records of 250 women with

untreated breast

cancers who were cared for on charity wards in

the Middlesex

Hospital, London, between 1805 and 1933

.

Slide8

Primary Breast Cancer.

More

than 80% of breast cancers show productive fibrosis that involves the epithelial and stromal tissues

.

entraps and shortens Cooper’s suspensory ligaments to

produce a

characteristic skin retraction

.

Localized edema (

peaud’orange

) develops

when drainage of lymph fluid from the skin is disrupted.

cancer cells invade the skin,

and eventually

ulceration occurs

.

As new areas of skin are invaded, small satellite nodules appear near the primary

ulceration.

Slide9

Axillary

Lymph Node Metastases

As

primary breast

cancer increases, some cancer cells are shed

into cellular

spaces and transported via the

lymphatics the

to the regional lymph nodes,

especially axillary LNs

.

LNs that

contain

mets

cancer

are at

first ill-defined and soft but become firm or hard with

continued growth

of the

mets

.

Eventually

LNs

adhere to each other and form a conglomerate mass

.

Cancer cells may grow through

LN capsule

and

fix to structures

in the axilla, including the chest wall

.

Slide10

Distant

Metastases

At approximately the twentieth cell

doubling, breast

cancers acquire their own blood supply (neovascularization).

Thereafter, cancer cells may be shed directly

into the

systemic venous blood to seed the pulmonary

circulation via

the axillary and intercostal veins or the vertebral

column.

These cells are scavenged by natural

killer lymphocytes

and macrophages

.

Successful

mets

foci

from breast cancer predictably occurs after the

primary cancer

exceeds 0.5 cm in diameter, which corresponds

to the

twenty-seventh cell doubling

.

For 10 years after initial

treatment, distant

metastases are the most common cause of death

in breast

cancer patients.

Metastases may

become evident as late as 20 to 30 years after

treatment

Common sites of

involvement, in order of frequency, are bone, lung,

pleura, soft

tissues, and liver. Brain metastases are less

Slide11

HISTOPATHOLOGY OF BREAST CANCER

Carcinoma

In Situ

Cancer cells are in situ or invasive depending on whether or

not they

invade through the basement membrane

.

ductal and

alveolar.

Lobular Carcinoma In Situ.

LCIS:

originates from the

terminal duct

lobular units and develops only in the female

breast

.

Ductal Carcinoma In Situ (DCIS): Although DCIS is

predominantly seen

in the female breast, it accounts for 5% of male breast cancers. Histologically, DCIS is

characterized by

a proliferation of the epithelium that lines the minor

ducts, resulting

in papillary growths within the duct

lumina

.

Slide12

HISTOPATHOLOGY OF BREAST CANCER

Invasive

Breast

Carcinoma

ldescribed

as lobular or

ductal in

origin

.

invasive ductal carcinoma of

no

special

type (NST).

Foote and Stewart originally proposed the following

classification for

invasive breast cancer125:

1. Paget’s disease of the nipple

2. Invasive ductal carcinoma—Adenocarcinoma with productive

fibrosis (

scirrhous

, simplex, NST), 80%

3. Medullary carcinoma, 4%

4. Mucinous (colloid) carcinoma, 2%

5. Papillary carcinoma, 2%

6. Tubular carcinoma, 2%

7. Invasive lobular carcinoma, 10%

8. Rare cancers (adenoid cystic, squamous cell, apocrine)

Slide13

Paget’s disease of the nipple

:

frequently presents

as a chronic, eczematous eruption

of the nipple, which

may be subtle but may progress to an ulcerated,

weeping lesion

. Paget’s disease usually is associated with extensive

DCIS and

may be associated with an invasive cancer.

Invasive ductal carcinoma of the breast with

productive fibrosis

(

scirrhous

, simplex, NST

):

accounts

accounts

for

80

% of

breast cancers.

Medullary carcinoma

is a special-type breast cancer; it

Accounts

for 4%. Grossly, the

cancer is

soft and hemorrhagic. A rapid increase in size may

occur secondary

to necrosis and hemorrhage.

Bilaterality

is reported in 20% of cases

.

Mucinous carcinoma (colloid carcinoma

),:

another

specialtype

breast

cancer, accounts for 2% of all invasive breast cancers. defined by extracellular pools of

mucin.

Papillary

carcinoma:

accounts

for 2% of all invasive breast cancers.

defined by papillae with

fibrovascular

stalks and

multilayered epithelium. showed a low frequency of axillary lymph node metastases

Slide14

Tubular

carcinoma:

accounts

for 2%. Under low-power magnification, a haphazard array of

small, randomly

arranged tubular elements is seen

.

Invasive lobular

carcinoma:

accounts for 10%. It is frequently multifocal,

multicentric

, and bilateral.

Slide15

DIAGNOSIS OF BREAST CANCER

Discussed in benign breast disorders.

Hx

Physical Examination

Investigations.

Slide16

Breast

Cancer Staging

The clinical stage of breast cancer is determined

primarily through

physical examination of the skin, breast tissue,

and regional

lymph nodes (axillary, supraclavicular, and

internal mammary).

Ultrasound

(US) is more sensitive than physical

examination alone

in determining axillary lymph

node involvement.

Fine-needle

aspiration (FNA

) or core biopsy of

sonographically

indeterminate

or suspicious

lymph nodes can provide a more definitive

diagnosis than

US alone

.

Sentinel

node dissection is the preferred method for

staging of

the regional lymph nodes in women with

clinically node-negative

invasive breast cancer. Axillary

dissection may

be avoided in women with 1 to 2 positive

sentinel nodes

who are treated with breast conserving

surgery.

whole breast radiation and systemic

therapy.A

frequently used staging system is the

TNM (tumor

, nodes, and metastasis) system

.

Slide17

Slide18

SURGICAL APPROACHES TO CANCER THERAPY

Multidisciplinary Approach to Cancer

Although surgery is an effective therapy for most solid

tumors, patients

who die from cancer usually die of metastatic disease.

In most instances, a multidisciplinary approach

beginning at

the patient’s initial presentation is likely to yield the

best result.

Slide19

Surgical Management of Primary Tumors

The goal of surgical therapy for cancer is to achieve

oncologic cure

.

A curative operation presupposes that the tumor is

confined to

the organ of origin or to the organ and the

regional lymph

node basin.

Patients in whom the primary tumor is

not

resectable

with negative surgical margins are considered to

have inoperable

disease.

The operability of primary tumors is

best determined

before surgery with appropriate imaging

studies.

Disease

involving multiple

distant metastases is deemed inoperable because it

is usually

not curable with surgery of

th

primary

tumor.

On occasion, primary tumors are resected in

these patients

for palliative reasons

,

Slide20

It is

important to determine optimum surgical margins for

each cancer

type so that adjuvant radiation and systemic therapy

can be

offered to patients

There

are also ongoing studies on

approaches to

assess margins intraoperatively, to allow immediate

intraoperative

reexcisions

as needed, and maximizing local control

.

Slide21

Surgical

Management of the Regional

Lymph Node

Basin

Most neoplasms have the ability

to metastasize

via the lymphatics.

most oncologic operations have been

designed to

remove the primary tumor and draining lymphatics

en

bloc.

Surgical management of the clinically negative

regional lymph

node

has

evolved with

the introduction

of

lymphatic mapping technology.

Lymphatic mapping

and sentinel lymph node biopsy specimen were first reported

in 1977 by Cabanas for penile

cancer.

Now, sentinel

node biopsy

specimen is the standard of care for the management

of melanoma

and breast cancer.

The first node to receive drainage from the tumor site

is termed

the sentinel node

.

It is the node most likely

to contain

metastases, if metastases to that regional lymph

node

are present.

Slide22

Slide23

Surgical

Management of Distant Metastases

The treatment of a patient with distant metastases depends

on the

number and sites of metastases, the cancer type, the

rate of

tumor growth, the previous treatments delivered and

the responses

to these treatments, and the patient’s age,

physical condition

, and desires

.

Slide24

CHEMOTHERAPY

Clinical Use of Chemotherapy

In patients with documented distant metastatic disease,

chemotherapy is

usually the primary modality of therapy.

Adjuvant therapy can be administered after surgery (postoperative chemotherapy), or before surgery (preoperative

chemotherapy neoadjuvant

chemotherapy, or

inductio

therapy

).

Chemotherapy destroys cells by first-order kinetics,

which means

that with

the administration

of a drug a

constan

percentage of

cells is killed, not a constant number of cells.

Cell- cycle

phase-nonspecific agents (e.g., alkylating

agents) have

a linear dose-response curve, such that the fraction of

cells killed

increases with the dose of the drug

.

In contrast,

the cell-cycle

phase-specific drugs have a plateau with respect

to cell

killing ability, and cell kill will not increase with

further increases

in drug dose.

Slide25

Anticancer

Agents:

Alkylating Agents

Antitumor Antibiotics.

Antimetabolites.

Plant Alkaloids.

Combination Chemotherapy

Slide26

RADIATION THERAPY

Radiation

therapy may be used as the primary

modality for

palliation in certain patients with metastatic disease,

primarily patients

with bony metastases.

Adjuvant radiation therapy can

be given

before surgery, after surgery, or, in selected cases,

during surgery

.

Slide27

HORMONAL

THERAPY

The first attempts at hormonal therapy were through

surgical ablation

of the organ producing the hormones involved,

such as

oophorectomy for breast cancer.

Currently, hormonal

anticancer agents

include androgens, antiandrogens,

antiestrogens, estrogens

, glucocorticoids, gonadotropin inhibitors,

progestins

.

such

as with the estrogen antagonist tamoxifen.

In breast cancer, estrogen and progesterone receptor

status is

used to predict the success of hormonal therapy.

Androgen receptor

is also being pursued as a therapeutic target

for

breast cancer

treatment.

Slide28

TARGETED

THERAPY

: Over

the past decade, increased understanding of cancer

biologyhas

fostered the emerging field of molecular

therapeutics.The

basic principle of molecular therapeutics is to exploit

themolecular

differences between normal cells and cancer cells

todevelop

targeted therapies.

IMMUNOTHERAPY

:

The

aim of immunotherapy is to induce or potentiate

inherent antitumor

immunity that can destroy cancer cells.

GENE

THERAPY:

Gene

therapy is being pursued as a possible approach to

modifying the

genetic program of cancer cells as well as treating

metabolic diseases

.

Slide29

Breast

Cancer Prognosis

Survival rates for women diagnosed with breast cancer in

the United

States can be obtained from the SEER Program of

the National

Cancer Institute.

The overall 5-year

relative survival

for breast cancer patients from the time period

of 2003–2009

from 18 SEER geographic areas

was 89.2

%.

The 5-year

relative survival by race was reported to be 90.4%

for white

women and 78.7% for black women.

The 5-year

survival rate

for patients with localized disease (61% of patients)

is 98.6

%; for patients with regional disease (32% of patients

), 84.4

%; and for patients with distant metastatic disease (

5% of

patients), 24.3%.

Slide30

Local-Regional

Recurrence

Women

with local-regional recurrence of breast cancer

may be

separated into two groups: those who have had

mastectomy and

those who have had lumpectomy.

Women

treated previously

with mastectomy undergo surgical resection

of the

local-regional recurrence and

appropriat

reconstruction. Chemotherapy and antiestrogen therapy are considered,

and adjuvant

radiation therapy is given if the chest wall has not

previously received

radiation therapy or if the radiation

oncologist feels that

there is

scope for

further radiation therapy, particularly if this is palliative.

Women treated previously with a breast conservation

procedure undergo

a mastectomy and appropriate

reconstruction. Chemotherapy and

antiestrogen therapy are considered.

Slide31

Slide32

Local-Regional Recurrence:

Women with local-regional recurrence of breast cancer

may be

separated into two groups: those who have had

mastectomy and

those who have had lumpectomy.

Women

treated previously

with mastectomy undergo surgical resection

of the

local-regional recurrence and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered,

and adjuvant

radiation therapy is given if the chest wall has not

previously received

radiation therapy or if the radiation

oncologist there

is

scope for

further radiation therapy, particularly if this is palliative.

Women treated previously with a breast conservation

procedure undergo

a mastectomy and appropriate reconstruction.

Chemotherapy and

antiestrogen therapy are

considered.

Slide33

SURGICAL

TECHNIQUES IN BREAST CANCER THERAPY

Excisional

Biopsy with Needle Localization

Excisional biopsy implies complete removal of a breast

lesion with

a margin of normal-appearing breast tissue.

important to consider the options for local therapy (

lumpectomy vs

. mastectomy with or without reconstruction) and the need

for nodal

assessment with SLN dissection.

After excision of a suspicious breast lesion, the

specimen should

be x-rayed to confirm the lesion has been excised

with appropriate

margins.

Slide34

Breast

Conservation

Breast conservation involves resection of the primary

breast cancer

with a margin of normal-appearing breast tissue,

adjuvant radiation

therapy, and assessment of regional lymph node status.

Resection of the primary breast cancer is

alternatively called

segmental mastectomy, lumpectomy, partial

mastectomy, wide

local excision, and

tylectomy

.

Slide35

Mastectomy

and Axillary Dissection

A skin-sparing mastectomy removes all breast tissue,

the nipple-areola

complex, and scars from any prior biopsy procedures

A total (simple)

mastectomy without

skin sparing removes all breast tissue, the

nipple-areola complex

, and skin.

An extended simple mastectomy

removes all

breast tissue, the nipple-areola complex, skin, and the level

I axillary

lymph nodes.

A modified radical (‘

Patey

’)

mastectomy removes

all breast tissue, the nipple-areola complex,

skin, and

the levels I, II and III axillary lymph nodes: the

pectoralis minor

which was divided and removed by

Patey

may be

simply divided

, giving improved access to level III nodes, and then

left in-situ

or occasionally the axillary clearance can

be performed without

dividing pectoralis minor.

The Halsted radical mastectomy

Nipple-areolar sparing mastectomy

Slide36