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BREAST - II

Ma. Salome F. Fernandez, MD, FPCS, FPSGS


BENIGN BREAST DISEASES
Fibrocystic Disease

• Exaggerated response of normal breast stroma


and epithelium to circulating and normally
produced hormones and growth factors

• Incidence:
• Age 30-40 years
• (but may persist into the 8th decade)
Fibrocystic Disease

• Presentation:
• Breast pain,
swelling, tenderness
• Frequently bilateral

• Not associated with


increased risk of breast CA
unless biopsy specimen
reveals ductal or lobular
hyperplasia with atypia
Fibrocystic Disease

🌸 Synonyms include:
•Fibrocystic changes
•Cystic mastopathy
•Chronic cystic disease
•Chronic cystic mastitis
•Schimmelbusch’s
disease
•Mazoplasia
•Cooper’s disease
•Reclus’ disease
•Fibroadenomatosis
Approach to a Breast Cyst

COMPLEX CYST or
SOLID MASS

Do CORE NEEDLE
BIOPSY

F/U in 6 months
BENIGN BREAST DISEASES
COMPLEX CYST or
SOLID MASS

Do CORE NEEDLE
BIOPSY

If PATHOLOGY is:
• Indeterminate
• LCIS
• Atypical hyperplasia
• Radial scar
• Papilloma

EXCISION BIOPSY to
make sure there is no
underlying DCIS or CA
Fibrocystic Disease Treatment

• Reassurance since it is NOT premalignant

• Pain management

• Aspiration of cystic lesion or excisional biopsy IF:


• If any discrete mass persists without change
over several monthly cycles
Fibrocystic Disease Treatment
🌸 FOR PAIN:

•Danazol, a weak androgen


•50-200 mg po BID for severe symptoms
•Must be continued to 2-3 months to see a potential
effect
•50% recurrence within 1 year of discontinuing the drug
•S/E: amenorrhea, body fat redistribution, weight gain,
acne, hirsutism

•Tamoxifen
•20 mg po QID for severe symptoms
•Anti-estrogenic; binds estrogen receptors
•Administer 4-6 wk course, then d/c to assess for
continued symptoms
Fibrocystic Disease Treatment

• ADVISE:

• Frequent breast examinations (BSE and MD)


• Baseline MMG for ages 35-39
• Annual MMG for women older than 40 to
identify any new or changing lesions
• Avoid xanthine-containing products (coffee, tea,
chocolate, cola drinks)
Fibroadenoma
Fibroadenoma

•INCIDENCE:
•Most common breast lesion
in women under age 30

•HISTOLOGY:
•Fibrous stroma surrounds
duct-like epithelium

•PRESENTATION:
•Grossly smooth, well-
circumscribed, nontender
mass 1-5 cm in diameter
Fibroadenoma

•NOT premalignant

•Lesions >5 cm are referred to


as giant fibroadenomas, must
be differentiated from
cystosarcoma phyllodes

•Is also estrogen-sensitive,


which has increased
tenderness during pregnancy

•The breast exam shows


smooth, discrete, circular and
mobile mass
Fibroadenoma

🌸 TREATMENT:
• Below 25 y/o -
Observation
• Age 25-35 y/o -
Observation/ Excision
• Age 35 y/o - Excision
Giant Fibroadenoma

🌸  Fibroadenomas very rarely turns malignant. 

• But when acquires a large size to be called as


giant fibroadenoma may have associated features of
malignancy; the reason why, it should be subjected
to histopathological study after removal.

• Removal of giant fibroadenomas may require removal


of a large chunk of normal breast tissue and sometimes
removal of the whole breast. 
16
Plan
! Reduction mammoplasty with free-nipple graft

! Bilateral mastectomy
Procedure
! Bilateral mastectomy (March 26, 2013)
Histopathology Report
! Bilateral giant fibroadenoma with fibrocystic change

! Tubular adenoma, right


Phylloides Tumors

🌸 Classified as:
• Benign
• Borderline
• Malignant

• Borderline tumors have a greater potential for local


recurrence

• Mesenchymal and epithelial components

• Rarely metastasize to axillary nodes


Phylloides Tumors
🌸 The breast exam:
• Large, bulky mass;
• Overlying skin is red, warm and shiny, with
venous engorgement
• Medium size of 4-5 cm; characterized by rapid growth
• Diagnosis: Biopsy with pathologic evaluation
• Treatment:
– Small Tumors: Wide local excision with a least a 1
cm margin
– Larger Tumors: Simple mastectomy
• Axillary dissection is not recommended because
axillary LN metastases rarely occur
Phylloides Tumors

• Large, bulky mass;


overlying skin is red,
warm and shiny, with
venous engorgement
Phylloides Tumors
Intraductal papilloma
🌸 Benign local proliferation of ductal epithelial cells
🌸 Presentations:
• Unilateral serosanguineous or bloody nipple discharge in
premenopausal women.
• Subareolar mass and/or spontaneous nipple discharge ➡
must radially compress breast to determine which
lactiferous duct express fluid

• Major DDx is between intraductal papilloma and invasive


papillary CA
• Diagnosis: Definitive diagnosis by pathologic evaluation of
resected specimen.
• Treatment: Excise affected duct after localization by PE
Intraductal papilloma
Gynecomastia
• The development of female-like breast tissue in males
• Can either be physiologic or pathologic.
• At least a 2 cm of excess subareolar breast tissue should be
present to make the diagnosis.

• Physiologic:
– Newborns: due to exposure to maternal estrogens
– Pubertal (ages 13-17) may be bilateral or unilateral; regresses
with adulthood; treated with reassurance
– Senescent (>age 50) due to male “menopause” with relative
estrogen increase; freq. unilateral; breast tissue is enlarged,
firm and tender; usually regresses spontaneously in 6-12
months
Gynecomastia

• Drug-induced

• Associated with use of estrogens, digoxin,
thiazides, phenothiazines, phenytoin,
theophylline, cimetidine, reserpine,
spironolactone, methyldopa, diazepam,
tricyclics, antineoplastic drugs, marijuana;

• Tx is discontinuation of offending drug.


Gynecomastia

• Pathologic: associated with cirrhosis, renal


failure, malnutrition, hyperthyroidism, adrenal
dysfunction, testicular tumors, hermaphroditism,
hypogonadism (eg. Klinefelter’s syndrome)

• Treatment: Treat underlying cause if specific


cause identified; any dominant or suspicious
mass should be biopsied to rule out carcinoma,
esp. in the senescent male.
Gynecomastia
Sclerosing Adenosis

• Benign (non-cancerous) condition of the breast

• Extra tissue develops within the breast lobules 

• Its clinical significance lies in its mimicry of cancer on PE,


mammography, and at gross pathologic exam.

• Excisional biopsy and histologic exam are frequently necessary


to exclude the dx of cancer.

• The diagnostic work-up for radial scars and complex sclerosing


lesions frequently involves stereotactic biopsy.
Sclerosing Adenosis
• Usually NOT possible to
differentiate these lesions
with certainty from CA by
mammogram, so biopsy is
recommended.

• Breasts radiologists
therefore often forego
image-guided needle
biopsy of a lesion
suspicious for radial scar
and refer the case directly
to a surgeon for wire
localized excision biopsy.
Sclerosing Adenosis
Atypical Ductal Hyperplasia

• A condition that can occur in the lining of the milk ducts in


the breast.
• Typically BENIGN in both males and females but can be at
risk for developing cancer; hence, further studies are needed.
• In women ➡ it rarely proceeds towards cancer
• In men ➡ when diagnosed with a background of
gynecomastia, is a 4-5 times increased risk for the
development of invasive breast carcinoma.
• Some may be an under-diagnosed ductal carcinoma in situ.
• Diagnosis: Biopsy
• Treatment:
• Observation, or Excisional Biopsy – do not need clear
margins
Atypical Ductal Hyperplasia
Atypical Ductal Hyperplasia
Mondor's Disease

• Painful superficial thrombophlebitis


– Thrombophlebitis of superficial veins of the chest
wall (thoracoepigastric vein)

• Presents as acute pain over superolateral breast or axilla

• Often related to local trauma

• Finding of palpable cord is diagnostic.

• Treatment: Reassurance, heat, analgesics


Mondor's Disease
PREMALIGNANT DISEASES

• Ductal CA in situ

• Lobular CA in situ
Ductal CA in Situ
• Proliferation of ductal cells that spread through the
ductal system but lack the ability to invade the basement
membrane.

• It arises from the inner layer of epithelial cells in major


ducts.
Ductal CA in Situ

•More than ½ the cases occur after menopause


•Presentation:
•Palpable mass is (rare)
•Mammographically detected mass

•Risk of invasive cancer:


• There is increased risk in ipsilateral breast,
usually SAME quadrant - where infiltrating
ductal carcinoma is most common histologic
type.
Ductal CA in Situ

• DIAGNOSIS:

•Mammogram: Clustered microcalcifications


•Stereotactic core needle biopsy of suspicious
calcifications:
•(+) Malignant epithelial cells in breast duct
•Wire localized excisional biopsy
•If calcifications of interest are not amenable
to stereotactic core needle biopsy:
•Proximity to chest wall, skin, or
cosmetic breast implant
Invasive Ductal CA

• Classification based on HISTOLOGIC FORMS:


• Scirrhous
• Medullary
• Comedo
• Colloid
• Papillary
• Tubular

• Classification based on NUCLEAR FEATURES:


• Low-grade
• Intermediate-grade
• High-grade
Invasive Ductal CA

• Classification based on HISTOLOGIC FORMS:


•Medullary:
•Forms a distinct boundary between tumor tissue and
normal tissue

•Colloid:
•Formed by mucus producing cancer cells

• Papillary and micropapillary types


• Have multiple projections with fibrovascular stalks.
• Papillary projections fuse to form Roman bridges
across the duct lumen.
• Most of these types have low nuclear grade.
Lobular CA In Situ (LCIS)

•DIAGNOSIS:
•Typically a clinically occult lesion,
undetectable by mammogram and
incidental on biopsy

•RISK of invasive cancer:


•Equally increased risk in either breast
(infiltrating ductal carcinoma)
•Associated with simultaneous LCIS in
the contralateral breast in over ½ of
cases
Invasive Ductal CA

• Classification based on HISTOLOGIC FORMS:


•Cribriform
•Tumor cells arranged in a sievelike pattern with
multiple small round glands growing within a gland
or duct.
•Glands are confluent without fibrous walls.
•Most of these tumor cells have low nuclear grade

•Solid-type DCIS
•Characterized by tumor cells filling the ducts as
solid sheets.
•Nuclear grade is usually intermediate or high.
•Focal necrosis may be present in this type.
Invasive Ductal CA

• Classification based on HISTOLOGIC FORMS:


•Comedo DCIS
•Usually has a solid growth pattern with CENTRAL
NECROSIS as a prominent feature.
•Calcification occurs within the central necrotic cellular
debris.
•Have high nuclear grade

• Noncomedo DCIS
• All subtypes that lack central necrotic cellular debris

🌸 Comedo necrosis correlates with increased risk of local


recurrence and invasion.
Invasive Ductal CA

• Classification based on NUCLEAR FEATURES:

• Low-grade
• Nuclear size of 1.0 to 1.5x the size of a red
blood cell
• Uniform size and shape of nuclei
• Fine granular chromatin
• Small nucleoli
• Low mitotic activity
Invasive Ductal CA

• Classification based on NUCLEAR FEATURES:

• Intermediate -grade
• Nuclear size up to 2x the size of red blood cell
• Mild to moderate variation in nuclear size and
shape
• Coarsely granular chromatin with even
distribution
• Nucleoli small to medium sized
• Mitotic activity between low and high grade
Invasive Ductal CA

• Classification based on NUCLEAR FEATURES:

• High-grade
• Nuclear size >2x the diameter of a red blood
cell
• Marked variation in nuclear size and shape
• Coarsely granular chromatin unevenly
distributed
• Large and multiple nucleoli
• High mitotic activity
Ductal CA in Situ

• TREATMENT:

•If small (< 2 cm):


•Lumpectomy with either close follow-up or
radiation

•If large (> 2 cm):


•Lumpectomy with 1 cm margins and radiation

•If breast diffusely involved:


•Simple mastectomy
Ductal CA in Situ

• TREATMENT:

•SIMPLE MASTECTOMY may be indicated for DCIS


when:
•Multicentric disease is present
•When there are large lesions, i.e., greater than 4
cm
•Central disease
•Persistent positive margins when attempting
breast-conserving surgery, or patient preference;
•When radiation is contraindicated
Ductal CA in Situ

•Sentinel node biopsy for DCIS


•Is generally unnecessary for DCIS, but can be done:
# After a CORE BIOPSY which has secured the diagnosis of DCIS
•there may be as much as a 20% chance of finding an
invasive cancer on removal of the lumpectomy specimen

$ At the time of LUMPECTOMY


•if the patient wishes to avoid a second operation

% At time of simple mastectomy


•if an invasive tumor is found in the specimen, an axillary
node dissection will be required and may be difficult if
reconstruction has been completed
Lobular CA In Situ (LCIS)

•Multifocal proliferation of
acinar and terminal ductal
cells

•Arises from cells of the


terminal duct-lobular unit

•Majority of cases occur


prior to menopause,

•Usually with NO palpable


mass
Lobular CA In Situ (LCIS)

TREATMENT OPTIONS:

1. Observation alone
2. Chemoprevention with
Tamoxifen
3. Prophylactic bilateral
mastectomy
MALIGNANT
DISEASES
of the
BREAST
MALIGNANT/ INVASIVE DISEASES

• Infiltrating Ductal CA

• Infiltrating Lobular CA

• Paget's Disease of the Nipple

• Inflammatory Breast CA
Invasive Ductal CA

•Most common invasive cancer in both males and


females (80% of cases)
•Most common in perimenopausal and
postmenopausal women
•PRESENTATION:
•Hard, fixed mass
•“peau d’ orange”
•Ulceration of overlying skin
•Bloody nipple discharge
•Inverted or retracted nipple
Infiltrating Lobular CA

•Second most common type of


invasive breast cancer

•It originates from terminal


ducts cells
•Like LCIS, has a high
likelihood of being
bilateral

•20% of infiltrating lobular


carcinoma have simultaneous
contralateral breast cancer
Infiltrating Lobular CA

•CLINICAL PRESENTATION:

•Ill-defined thickening of the breast

•Like LCIS, does not form


microcalcifications and is often
multicentric

•Tends to metastasize to the axilla,


meninges, and serosal surfaces.
Paget’s Disease of the Nipple
Paget’s Disease of the Nipple

•2% of invasive breast cancers

•Usually associated with underlying LCIS


or ductal carcinoma just beneath the
nipple and areola.

•Presentation:
•Tender, eczematous, itchy nipple
with or without a bloody
discharge with or without a
subareolar palpable mass

• Treatment:
• Usually requires a modified
radical mastectomy.
Paget’s Disease of the Nipple
Paget’s Disease of the Nipple
Inflammatory Breast CA

•Most rapidly lethal


malignancy of the
breast

•Poorly-differentiated

•Characterized by
dermal lymphatic
invasion on
pathological exam
Inflammatory Breast CA
•PE:
•Diffuse induration,
warm, erythematous,
“peau de orange” skin
of the breast
•With or without
palpable mass
•Axillary
lymphadenopathy is
almost always present

•Distant metastases common


at time of diagnosis
Inflammatory Breast CA
Inflammatory Breast CA
Sentinel LN Biopsy (SLNB)

•Used to provide staging information and to determine


the need for axillary lymph node dissection (ALND) in
breast cancer patients

•A properly performed negative SLNB should


accurately identify those patients without axillary
node involvement, thereby obviating the need for a
more morbid ALND

•The risk of arm morbidity, particularly lymphedema, is
significantly lower after SLNB than ALND.
Sentinel LN Biopsy (SLNB)

•Should be performed in most women with clinically


node negative invasive or microinvasive breast
cancer

•SLNB can be omitted if the nodal information will


not affect adjuvant treatment decisions.
•Example, women ≥70 years of age who have
a small (<2 cm) estrogen receptor-positive
tumor and a clinically uninvolved axilla may
be treated without a SLNB.
Sentinel LN Biopsy (SLNB)

•SLNB should be performed in women with extensive


DCIS who are undergoing mastectomy.
•SLNB will not be possible after mastectomy if
invasive disease is found on final pathology,
necessitating an axillary dissection for staging
purposes

•When a SLNB is not successful or when clinically


suspicious nodes are encountered in the axilla the
surgeon should perform an axillary dissection for
staging purposes and to ensure locoregional control
Sentinel LN Biopsy (SLNB)

•A radioactive •The injected •The sentinel nodes


substance and/or material is detected (the first lymph
visually and/or with nodes to take up
blue dye is
a probe that the material) are
injected near the detects
tumor (first removed and
radioactivity
checked for cancer
panel) (middle panel).
cells (last panel).
SURGICAL TREATMENTS for Breast CA

1. Wide Local Excision (WLE)/ Lumpectomy/ Segmental


Mastectomy
2. Subcutaneous Mastectomy
3. Simple Mastectomy/ Total Mastectomy
4. Modified Radical Mastectomy (MRM)
5. Radical Mastectomy (Halsted) (RM)
Wide Local Excision/ Lumpectomy

•Also “segmental mastectomy”

•Breast-conserving therapy

•Major objectives:
•Complete excision of the tumor with tumor-free margins
•Good cosmetic result

•Usually accompanied by axillary node dissection (through a


separate incision) and radiation therapy to the whole breast post-
op.
Wide Local Excision/ Lumpectomy

•Eligibility Criteria:

•Tumor size 4cm or less


•Appropriate tumor size to breast size ratio
•No fixation of tumor to underlying muscle or chest
wall
•No involvement of overlying skin
•No multicentric cancer
•No fixed or matted axillary nodes
Wide Local Excision/ Lumpectomy

• Complete excision of
tumor with tumor-free
margins

• Usually accompanied by
axillary node dissection
(through a separate
incision) and radiation
therapy to the whole
breast post-op

• Curvilinear incision in
upper quadrants, radial
incisions in the lower
quadrants
Subcutaneous Mastectomy

•Removes breast tissue only, sparing the nipple-areolar complex,


skin and nodes
•Not a cancer operation, leaves 1-2% of breast tissue behind
•Rarely, if ever, indicated.
•Mainly a PROPHYLACTIC operation
•A unilateral S.C.M. is indicated in patients who have already had
a mastectomy for carcinoma and whose remaining breast has an
increased risk for also developing a carcinoma.
•May be performed according to total mastectomy indications if
an intraoperative frozen section (and the corresponding HE
histopathology) of the tissue next to the nipple-areola skin is
free of tumor.
Simple/ Total Mastectomy

• Removes the breast


tissue, the nipple-areolar
complex, and skin
• No axillary node
dissection /minimal
axillary node dissection is
performed
• Often performed for DCIS
or LCIS
Modified Radical Mastectomy (MRM)

• Removes
• Breast tissue
• Pectoralis fascia
• Nipple-areolar complex
• Skin
• Axillary lymph nodes in continuity

• Spares the pectoralis major muscle


Modified Radical Mastectomy (MRM)

• 2 types:

•Patey procedure:
•Preserves the pectoralis major
•Removes the pectoralis minor in order to remove Levels I, II
and III axillary lymph nodes

•Auchincloss procedure:
•Preserves both pectoralis major and pectoralis minor
muscles.
•Preservation of pectoralis minor limits high axillary node
dissection (Level III), but this does not seem to be clinically
significant in most cases.
Modified Radical Mastectomy (MRM)
Modified Radical Mastectomy (MRM)

85
Simple Mastectomy 

and Modified Radical Mastectomy
• A simple, or total,
mastectomy (left)
removes the breast
tissue, nipple, areola and
skin, but not all the
lymph nodes. A modified
radical mastectomy
(right) removes the entire
breast, including the
breast tissue, nipple,
areola and skin, and most
of the underarm (axillary)
lymph nodes.

86
Post-operative Care after Mastectomy

87
Radical Mastectomy (Halsted) (RM)
• Removes breast tissue, nipple-areolar complex,
skin, pectoralis major and minor, and axillary
lymph nodes in continuity.
• Leaves bare chest wall with significant cosmetic
and functional deformity.
• Of historical interest only; Clinical trials
comparing MRM with RM reveal no significant
difference in disease-free survival, distant
disease-free survival, or overall survival.

88
Radical Mastectomy (Halsted) (RM)

• Removes breast
tissue, nipple-areolar
complex, skin,
pectoralis major and
minor, and axillary
lymph nodes in
continuity.
• Leaves bare chest
wall with significant
cosmetic and
functional deformity.

89
Different Types of Mastectomies

90
BREAST CANCER
Maria Salome Fernandez, MD, FPCS, FPSGS
EARLY
INVASIVE
BREAST CA
(Stage I, IIA & IIB)
RISK FACTORS

7. Irradiation to chest
1. Family history 8. Germ- Line mutations

2. High dietary fat intake 1.) BRCA 1 Chrom. 17q21

3. Obesity 2.) BRCA 2 Chrom. 13q12-13

4. Late menopause (> 45) 9. Certain breast diseases

a. Atypical hyperplasia
5. Infertility & nulliparity
b. Lobular carcinoma in situ
6. History of primary breast CA
c. Ductal carcinoma in situ
• BreastCA is the second most common cause of
cancer death in women.

• EARLY STAGE BREAST CA:

• Confined to the loco-regional lymph nodes


and or breast

• No evidence of distant metastases.


TNM STAGING BREAST CA
TNM STAGING BREAST CA
Stage I (T1 N0 M0)
Stage I (T1 N0 M0)
T1: Tumor ≤ 2 cm
Stage IIA

T0 N1 M0

T1 N1 M0

T2 N0 M0
T0 N1 M0 T1 N1 M0 T2 N0 M0
PRIMARY TX of early stage invasive breast cancer is
comprised of:

1. Definite local treatment to remove the primary


tumor PLUS

2. Adjuvant local or systemic therapy to treat


microscopic residual disease.

• Adjuvant therapy: Reduces the risk of


recurrence and cancer-related mortality.
Stage IIB
T2 N1 M0
T3 N0 M0

T2: Tumor >2 <5 cm


T3: Tumor > 5 cm

N1: Metastasis to
movable ipsilateral
axillary LNs
T2 N1 M0
N1: axillary LN
T2 N1 M0 T3 N0 M0
movable
TREATMENT FOR EARLY BREAST CA

•FACTORS that influence the treatment of


localized breast cancer:

•Woman's age
•Menopausal status
•Tumor size
•Status of the axillary lymph nodes
•Hormone receptors expression and/or
the protein HER2
TREATMENT FOR EARLY BREAST CA

# Breast Conservation Therapy with axillary


staging
•Lumpectomy and radiation therapy

$ Mastectomy with axillary staging


TREATMENT FOR EARLY BREAST CA

# Breast Conservation Therapy with axillary staging

•Preferred method of treatment for women with


early stage breast cancer who have UNIFOCAL
disease and who are not known BRCA mutation
carriers

•Is considered for all patients because of the


important cosmetic advantages and equivalent
survival outcomes

•The addition of radiation not only improves local


control but also has an impact on survival.
TREATMENT FOR EARLY BREAST CA

# Breast Conservation Therapy with axillary staging

•Is NOT advised in women who are known BRCA


mutation carriers due to the high lifetime risk for
development of additional breast cancers

•RELATIVE CONTRAINDICATIONS to breast


conservation therapy
(a) Prior radiation therapy to the breast or chest
wall
(b)Persistently positive surgical margins after
reexcision
(c) Multicentric disease
(d) Scleroderma or lupus erythematosus
TREATMENT FOR EARLY BREAST CA

•Subgroups of patients who may not benefit


from the addition of radiation therapy:

1. Older patients who may have a shorter


life expectancy due to medical
comorbidities

2. In selected patients with small, low-


grade tumors, lumpectomy alone with-
out radiation therapy may be
appropriate.
TREATMENT FOR EARLY BREAST CA

•Subgroups of patients who may NOT benefit from the addition


of radiation therapy:

3. Radiation can be avoided in early-stage breast cancer


patients >age of 70 when they are diagnosed with T1, N0, ER-
positive breast cancer
•Canadian trial of women 50 years and older and
randomized to lumpectomy with or without radiation.
•80% of women had ER-positive tumors.
•Local recurrence rates were lower in women
who received radiation (0.6% vs. 7.7%,
P<0.001)
•However, at a median follow-up of 5.6 years,
there were NO DIFFERENCES in DFS or OS.
TREATMENT FOR EARLY BREAST CA

1-A Accelerated partial breast irradiation (APBI)

• Another option for carefully selected patients with


DCIS and early-stage breast cancer

• Since majority of recurrences after BCT occur in or


adjacent to the tumor bed —> APBI limits the
radiation to the area of the primary tumor bed with
a margin of normal tissue.
TREATMENT FOR EARLY BREAST CA

Accelerated partial breast irradiation (APBI)

• APBI is delivered in an abbreviated fashion:


• TWICE daily for 5 days
• At lower total dose
• (Standard course of 5 to 6 weeks of
radiation, 50 Gray with or without a
boost in the case of whole breast
irradiation)

• Proponents suggested that this shortened course


of treatment may increase feasibility of breast
conservation for some women and may improve
radiation therapy compliance
TREATMENT FOR EARLY BREAST CA

•The American Society for Radiation Oncology (ASTRO)


•Developed guidelines for the use of APBI outside of
clinical trials based on data reported from published
studies.

•The ASTRO guidelines describe patients “suitable”


for APBI to include:

1. Women 60 years of age or older with a unifocal,


T1, ER-positive tumor with no lymphovascular
invasion, and margins of at least 2 mm
TREATMENT FOR EARLY BREAST CA

•The ASTRO guidelines describe patients “suitable”


for APBI to include:

2. A group where there is uncertainty about the


appropriateness of APBI (“cautionary” group) to
include :

•Patients with invasive lobular histology


•Tumor size of 2.1 cm to 3 cm
•ER-negative disease
•Focal lymphpvascular invasion, or
•Margins less than 2 mm.
TREATMENT FOR EARLY BREAST CA

•The ASTRO guidelines describe patients “suitable” for


APBI to include:

3. A group felt to be “unsuitable” for APBI includes


those with:
•T3 or T4 disease
•ER-negative disease
•Multifocality
•Multicentricity
•Extensive LVI, or
•Positive margins.
TREATMENT FOR EARLY BREAST CA

% MASTECTOMY with axillary staging

• Main component of curative therapy for breast cancer

• Multiple randomized controlled trials showed:

• Equivalency of MASTECTOMY vs. breast


conservation surgery (BCS/BCT) plus radiation
therapy in women with early stage breast cancer.
TREATMENT FOR EARLY BREAST CA

•Patients with LARGE TUMORS that cannot be


treated by breast conservative approach are best
treated by MASTECTOMY

•PREOP SYSTEMIC TX (chemotherapy or


hormone therapy if hormone receptor
positive) followed by surgery is an alternative
approach for these patients (in an effort to
make breast conservation possible).
TREATMENT FOR EARLY BREAST CA

BREAST RECONSTRUCTION

•Immediate reconstruction can be performed using


implants or autologous tissue

•Tissue flaps commonly used:


•TRAM Flap
•transverse rectus abdominis myocutaneous
flap
•Deep inferior epigastric perforator flap
•Latissimus dorsi flap (with or without an implant)
TREATMENT FOR EARLY BREAST CA

BREAST RECONSTRUCTION

•Tissue expander
•Can be placed at the
time of mastectomy to
save the shape of the
breast and reduce the
amount of skin
replacement needed if
postmastectomy
radiation therapy is
needed, at the time of
definitive
reconstruction
TREATMENT FOR EARLY BREAST CA

BREAST RECONSTRUCTION

•Tissue expander
•Can be deflated at the initiation of radiation
therapy
• To allow for irradiation of the chest wall
and regional nodal basins.

•Removal of the tissue expander and definitive


reconstruction, usually with autologous tissue,
can proceed 6 months to 1 year after completion
of radiation therapy.
Management of Regional Lymph Nodes

Axillary node status is an important prognostic factor.

Early breast cancer:

Surgical assessment of axillary nodal status is required


to guide decisions on further therapy.
Management of Regional Lymph Nodes

SLNB: Sentinel Lymph Node Biopsy

Increasingly used to assess axillary LN status

Associated with lower rate of morbidity than full axillary


lymph node dissection.

American Society of Clinical Oncology (ASCO) recommend


SLNB as an alternative to axillary node dissection in women
with a clinically negative axilla.
Breast Radiation After Lumpectomy

•Radiation therapy (RT) with a boost to the lumpectomy cavity


•Standard component of breast conserving therapy
•May also be indicated after mastectomy

•Purpose of RT:
•To eradicate subclinical residual disease
•To minimize local recurrence rates.
Chest Wall Radiation After Mastectomy

•For women with HIGH-RISK DISEASE:

•(ie, large tumor size or involved lymph nodes)


•Reduces the risk of locoregional recurrence
•Reduces mortality from breast cancer
SYSTEMIC ADJUVANT TREATMENT

•Follows definitive local therapy for breast cancer:


1. Hormone therapy
2. Chemotherapy and/or
3. Trastuzumab (a humanized monoclonal antibody directed
against HER2)

•GOAL of systemic adjuvant therapy for Early Stage CA following


curative surgery:
•To treat micrometastases thereby reducing risk of
recurrence and cancer-related mortality.
SYSTEMIC ADJUVANT TREATMENT

•Choice of ADJUVANT TX depends on:

•Clinicopathologic factors:
•Presence or absence of nodal metastases
•Tumor size

•Biologic/ Molecular factors:


•Estrogen and Progesterone receptor (ER/PR) status
•HER2 overexpression
SYSTEMIC ADJUVANT TREATMENT

•Benefits the majority of women with early stage


breast cancer

•BUT the magnitude of benefit is greatest for women


with high risk disease.
1) Hormone Therapy

•In women with ER/PR positive early-stage breast cancer:


•Adjuvant HT reduces the risk of recurrence and mortality.

•ER and PR negative breast cancers DO NOT respond to hormone


therapy.
•Therefore, adjuvant hormone therapy is not indicated in
ER/PR negative breast cancer.
1) Hormone Therapy

•Women with OPERABLE ER/PR positive tumors:


•5 years of TAMOXIFEN reduces the risk of recurrence
on average by 41% and breast cancer mortality by
34%

•PREMENOPAUSAL women:
•5 years of TAMOXIFEN is the standard adjuvant
hormone therapy.
•Suppression of ovarian function is another effective
therapeutic option
1) Hormone Therapy

•POSTMENOPAUSAL women:
•3rd-generation AROMATASE INHIBITORS are superior to 5
years of adjuvant tamoxifen:
1. Anastrozole
2. Letrozole
3. Exemestane
•In such women, use of aromatase inhibitors is recommended
at some point in the adjuvant hormone treatment

•Aromatase inhibitors are NOT indicated in premenopausal women.


2) Chemotherapy

•ADJUVANT chemotherapy benefits BOTH


premenopausal and postmenopausal women
irrespective of hormone receptors status.

•Although absolute magnitude of benefit is


greater in:
•Younger > older women
•ER/PR negative > ER/PR positive
breast cancer.
2) Chemotherapy

•Early Breast Cancer Trialists' Collaborative Group


(EBCTCG) overview analysis:

•Adjuvant chemotherapy in women younger than


50:

•Reduces the risk of disease relapse and


death by 37 and 30 percent, respectively.

•➡ 10 % absolute improvement in 15-year


survival (42 vs. 32%)
2) Chemotherapy

•Early Breast Cancer Trialists' Collaborative Group


(EBCTCG) overview analysis:

•For women aged 50 to 69:

•Risk of relapse or death decreases by 19


and 12% respectively

•This translated into a 3 % absolute gain


in 15-year survival (50% vs. 47%)
2) Chemotherapy

•Early Breast Cancer Trialists' Collaborative Group


(EBCTCG) overview analysis:

•For women aged 70 years and older:

•The benefit of chemotherapy is


UNCERTAIN because few studies
included women in this age group.
2) Chemotherapy

•NEOADJUVANT CHEMOTHERAPY

•Chemotherapy prior to definitive local treatment

•INDICATIONS:

•Women with locally advanced or inflammatory


breast cancer
•May also be considered to facilitate breast
conservative surgery.
2) Chemotherapy

•COMBINATION CHEMOTHERAPY

•Adjuvant treatment of choice for women with hormone non-


responsive (ie, ER/PR negative) breast cancer who need
adjuvant therapy.

•Also appropriate for women with high risk ER positive


breast cancer, in conjunction with hormone therapy

•Anthracycline and taxane-based chemotherapy regimens


are commonly used in this setting.
3) Trastuzumab (Herceptin®)

•Early data from several randomized trials suggest:

•The addition of trastuzumab to anthracycline and


taxane-containing adjuvant chemotherapy regimens
provides substantial benefit for women with HER2-
positive breast cancer, both in terms of disease
recurrence and overall survival.

•Approximately 20 percent of breast cancers overexpress


the HER2 protein.
3) Trastuzumab (Herceptin®)

•Trastuzumab is recommended in addition to an


anthracycline and taxane-based regimen for:
•Women with HER2-overexpressing, node-positive
breast cancer, and
•Possibly for those with high-risk, node-negative
disease.

•It has been associated with an increase in the incidence of


both symptomatic as well as asymptomatic cardiac
dysfunction.
PROGNOSIS

•Approximately 50% of patients with operable breast cancer develop


recurrent disease UNLESS they receive adjuvant chemotherapy or
hormone therapy.

•Prognostic factors include:

•Tumor size
•Tumors larger than 5 cm are associated with a
decreased survival rate and increased recurrence
rate.
•Axillary node status
•Histopathology
•Hormone receptor status
•Oncogenic expression
5-year Survival According to Stage

STAGE 5- YEAR SURVIVAL RATE

I 92%

II 87%

III 75%

IV 13%
MOLECULAR SUBTYPES OF BREAST CA

•Five main intrinsic or molecular subtypes of breast cancer


that are based on the GENES a cancer expresses:

•Luminal A
•Luminal B
•Triple-negative/basal-like breast cancer
•HER2-enriched breast cancer
•Normal-like breast cancer
MOLECULAR SUBTYPES OF BREAST CA

•Luminal A breast cancer

•Hormone-receptor positive (ER and/or PR positive)


•HER2 negative
•Has low levels of the protein Ki-67, which helps
control how fast cancer cells grow.
•Are low-grade, tend to grow slowly
•Have the best prognosis
MOLECULAR SUBTYPES OF BREAST CA

•Luminal B

•Hormone-receptor positive (estrogen-receptor and/or


progesterone-receptor positive)
•Either HER2 positive or HER2 negative
•With high levels of Ki-67
•Generally grow slightly faster than luminal A cancers
and their prognosis is slightly worse
MOLECULAR SUBTYPES OF BREAST CA

•Triple-negative/basal-like breast cancer

•Hormone -receptor negative (estrogen-receptor and


progesterone-receptor negative)
•HER2 negative
•More common in women with BRCA1 gene mutations.
•This type of cancer also is more common among
younger and African-American women
MOLECULAR SUBTYPES OF BREAST CA

•HER2-enriched breast cancer

•Hormone-receptor negative
•HER2 positive
•Tend to grow faster than luminal cancers
•Can have a worse prognosis, but are often successfully treated
with targeted therapies aimed at the HER2 protein:

1. Herceptin (chemical name: trastuzumab),


2. Perjeta (chemical name: pertuzumab)
3. Tykerb (chemical name: lapatinib),
4. Kadcyla (chemical name: T-DM1 or ado-trastuzumab
emtansine)
MOLECULAR SUBTYPES OF BREAST CA

•Normal-like breast cancer

•Similar to luminal A disease:


•Hormone-receptor positive
•HER2 negative
•Has low levels of the protein Ki-67, which helps
control how fast cancer cells grow.

•Still, while normal-like breast cancer has a good


prognosis, its prognosis is slightly worse than luminal A
cancer’s prognosis.
SUMMARY

•Breast cancer is the most common female cancer, in contrast to


male where it is rare, with a ratio of 100:1

•Screening test of choice: Mammogram

•Diagnostic Test: Biopsies

•Treatments:
•Surgery
•Hormonal Therapy (Tamoxifen, Aromatase inhibitors)
•Adjuvant Therapy [Chemotherapy, Radiation Therapy]
•Targeted therapy (Trastuzumab)