Breast disease

1 – anatomy of breast and axilla
2 - risk assessment and management.
3 - benign breast diseases and management.
4 - screening and investigations.
5 - Breast cancer types, staging & prognosis
6 - Treatment of invasive breast cancer

outlines
 Risk factors for breast cancer.
 Classification of patients at risk (normal, low risk, moderate risk, high risk) & management.
 Online risk assessment tools (tyrer-cuzick, Gail, claus, Penn II, BRCAPRO, BOADICEA).
 Signs and symptoms of breast disease. (mastalgia, discharge, skin changes, nipple changes, mass).
 Rule of Screening mammogram & diagnostic mammogram.
 BIRADS.
 Rule of ultrasound.
 Rule of MRI.
 Rule of core needle biopsy (turcut biopsy).
 Rule of FNA.
 Rule of skin biopsy.
 Sterotactic biopsy, us guided biopsy, MRI guided biopsy.
 Benign breast lesions and appropriate management. (hyperplasia, proliferative without atypia, proliferative with atypia
(ADH, ALH), LCIS.
 Types of breast cancer (DCIS, invasive ductal CA, invasive lobular CA, inflammatory CA).
 Van-Nuys prognosit index (for DCIS only).
 Staging of breast CA
 Lumpectomy VS mastectomy
 SLND & ALND
 Radiation therapy.
 Hormonal therapy (SERM’s, AI’s)
 HER2/NEU antibody (trastuzumab)
 Chemotherapy.

1- Chest wall
2- Pectoralis muscles
3- Lobules
4-Nipple
5-Areola
6-Milk duct
7-Fatty tissue
8-Skin

Anatomy of breast
 In women, the breasts overlie the pectoralis major
muscles and usually extend from the level of the
second rib to the level of the sixth rib.
 the breast is composed of differing layers of tissue,
predominantly two types: adipose tissue; and
glandular tissue.
 The female adult breast contains 14–18 irregular
lactiferous lobes that converge at the nipple
 The terminal lactiferous ducts drain the milk from
terminal duct lobular units into 4–18 lactiferous ducts.
 Approximately 75% of the lymph from the breast
travels to the axillary lymph nodes.

axilla
 The axilla is a quadrangular space that lies between the
following:
- The lower border of the axillary vein superiorly
- The chest wall medially
- The axillary skin laterally
- Pectoralis major and minor anteriorly
- Latissimus dorsi, teres major, and subscapularis
posteriorly

axillary lymph nodes
 The axillary lymph nodes are arranged in six groups:
 Anterior (pectoral) group: Lying along the lower border of the pectoralis minor behind
the pectoralis major, these nodes receive lymph vessels from the lateral quadrants of the
breast and superficial vessels from the anterolateral abdominal wall above the level of the
umbilicus.
 Posterior (subscapular) group: Lying in front of the subscapularis muscle, these nodes
receive superficial lymph vessels from the back, down as far as the level of the iliac crests.
 Lateral group: Lying along the medial side of the axillary vein, these nodes receive most
of the lymph vessels of the upper limb (except those superficial vessels draining the
lateral side—see infraclavicular nodes, below).
 Central group: Lying in the center of the axilla in the axillary fat, these nodes receive
lymph from the above three groups.
 Infraclavicular (deltopectoral) group: These nodes are not strictly axillary nodes
because they are located outside the axilla. They lie in the groove between the deltoid
and pectoralis major muscles and receive superficial lymph vessels from the lateral side
of the hand, forearm, and arm.
 Apical group: Lying at the apex of the axilla at the lateral border of the 1st rib, these
nodes receive the efferent lymph vessels from all the other axillary nodes.

Axillary lymph node levels
 There are three levels of axillary lymph nodes:
- Level I is the bottom level, lateral to the lower edge of
the pectoralis minor muscle.
- Level II is lying underneath the pectoralis minor
muscle.
- Level III is medial to the pectoralis minor muscle.

Before we start…
 Any solid mass need biopsy regardless of age.
 Any mass (solid or cystic) in post-menopause patient need
biopsy.
 Cystic lesions in premenopausal need ultrasound to
determine the type of cyst (simple cyst, complex cyst,
complicated cyst) because the management differ
according to the type.
 DCIS is cancer without invasion to basement membrane.
 LCIS is not cancer, this is a wrong name for this condition,
LCIS is considered risk factor for breast CA.
 BRCA1 is associated with triple - tumors, BRCA2 usually
triple + or double + tumors.

 LCIS: lobular carcinoma in situ.
 ADH: atypical ductal hyperplasia.
 ALH: atypical lobular hyperplasia.
 FEA: flat epithelial atypia.
 DCIS: ductal carcinoma in situ.
 ALND: axillary lymph node dissection.
 SLNB: sentinel lymph node biopsy.
 BBD: Benign breast disease.

Risk factors for breast cancer
 1 in every 8 women will have breast cancer during
lifetime. 1/8 = 12.5%
 12.5% is the average risk to have breast cancer (normal
risk for any female).
 Risk above 12.5% is considered increased risk. (either
low risk, moderate or high risk).
 12.5% - 15% low risk.
 15% - 20% moderate risk.
 >20% high risk.
 How to calculate risk?

Risk factors
 The primary risk factors for breast cancer are being female and older age, self
or family history of breast CA or ovarian CA.
 Other potential risk factors include genetics, lack of childbearing or lack of
breastfeeding, early menarche, late menopause, hormonal replacement
therapy, previous radiation exposure, obesity, smoking, alcohol, lack of
physical activity.
 Previous biopsy with atypia or LCIS are considered risk factors.
 Genetic factors:
There are five well recognized syndromes associated with breast CA, these
include:
1- hereditary breast-ovarian cancer syndrome: (BRCA1, BRCA2 mutations).
2- Li–Fraumeni syndrome: (p53 gene mutation).
3- Cowden syndrome: (PTEN gene mutation).
4- Bannayan–Riley–Ruvalcaba syndrome: (PTEN gene mutation).
5- Peutz–Jeghers syndrome: (STK11 gene mutation).
 Other genetic mutations associated with breast ca include: CHEK2, ATM,
BRIP1, and PALB2 mutations.

Genetic risk factors:
 genetics is believed to be the primary cause of 5–10% of all cases of breast CA.
 Usually breast CA occur at younger age.
 Genetic mutations associated with breast CA include:
 BRCA1, BRCA2 mutation:
- BRCA are tumour suppressor genes, mutations in these genes may produce a hereditary
breast-ovarian cancer syndrome in affected persons.
- Approximately 50% to 65% of women born with a deleterious mutation in BRCA1 will
develop breast cancer by age 70, and 35% to 46% will develop ovarian cancer by age 70.
- Approximately 40% to 57% of women with a deleterious mutation in BRCA2 will develop
breast cancer by age 70, and 13% to 23% will develop ovarian cancer by age 70.
- BRCA1 is associated with triple-negative breast cancer, Breast cancer often appears about
two decades earlier than normal.
- BRCA2 is associated with triple-positive breast cancer, primarily with post-menopausal
breast cancer.
- Approximately 1% to 2% of men with a BRCA1 mutation will develop breast cancer by age
70. Approximately 6% of men with a BRCA2 mutation will develop breast cancer by age
70.

Genetic risk factors:
 Li–Fraumeni syndrome (LFS):
- germline mutations of the p53 tumor suppressor gene.
- The classical LFS malignancies: sarcoma, cancers of the breast, brain and adrenal glands.
- Early onset breast cancer accounts for 25% of all the cancers in this syndrome. This is followed by soft
tissue sarcomas (20%), bone sarcoma (15%) and brain tumors - especially glioblastomas - (13%). Other
tumours seen in this syndrome include leukemia, lymphoma and adrenocortical carcinoma.
 Cowden syndrome (also known as multiple hamartoma syndrome):
- autosomal dominant inherited condition associated with mutations in PTEN gene a tumor suppressor
gene. ***
- characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast,
thyroid, uterine, skin, colon cancers.
 Bannayan–Riley–Ruvalcaba syndrome: also PTEN gene mutation, associated with Breast, renal,
thyroid cancers.
 Peutz–Jeghers syndrome:
- is an autosomal dominant genetic disorder, the mutated gene known as STK11 (LKB1) is a possible
tumor suppressor gene.
- characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and
hyperpigmented macules on the lips and oral mucosa.
- patients with the syndrome have an increased risk of developing carcinomas of the liver, lungs, breast,
ovaries, uterus, testes and other organs.
*** PTEN gene mutation is associated with four syndromes, including:
Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, Bannayan–Riley–Ruvalcaba
syndrome

Genetic counseling
- Indications for genetic study include:
 A known mutation (BRCA1 or BRCA2) in a cancer susceptibility gene within the
family
 Women affected with any Breast cancer diagnosed under the age of 30.
 Women affected with triple negative breast cancer (TNBC) under the age of 50.
 Two relatives (FDR/SDR) diagnosed under the age of 45.
 Three relatives (FDR/SDR) diagnosed with average age of 50 or less
 Four relatives at any ages.
 Ovarian cancer with either an additional diagnosed relative or a relative with
male breast cancer
 A single family member with both breast and ovarian cancer
 Male breast cancer
 Pancreatic cancer with breast or ovarian cancer in the same individual or on the
same side of the family.
 Ashkenazi Jewish or Polish ancestry with one FDR family member affected by
breast or ovarian cancer at any age

 We calculate risk by taking full history including family
history and any previous breast biopsy and mammogram
findings.
 Gender and age are the most important risk factors.
 Medical History: important risk factors in history include:
age, age of menarche, age of menopause, age at first live
birth, breastfeeding, use of hormonal replacement therapy,
obesity, alcohol use, race (jewish) , radiation exposure,
personal history of breast CA or ovarian CA, 1st degree
family history of breast CA or ovarian CA, breast cancer in
male relative, etc…
 Online assessment tools are available to calculate the risk.
Risk assessment

Risk factors for breast cancer

Online risk assessment tools (tyrer-cuzick, Gail,
claus, BRCAPRO, BOADICEA).
 Many online tools can be used to calculate the life-
time risk for breast cancer.
 The most widely used tools in clinics are: tyrer-cuzick
“also known as IBIS tool”.
 The most widely used tool in large studies and
researches is the GAIL model “also known as bcrisk
tool”.

Gail model (bcrisk tool)
 Website: https://bcrisktool.cancer.gov/calculator.html
 Bcrisk tool does not include BRCA mutations and previous history of breast
cancer of high risk lesions in the assessment.
 The tool uses a woman’s own personal information to estimate risk of
developing invasive breast cancer over specific periods of time, including:
1- Age 2- Age at the start of menstruation
3- Age at first live birth of a child
4- Number of first-degree relative (mother, sisters, daughters) with breast cancer
5- Number of previous breast biopsies (whether positive or negative)
6- Presence of atypical hyperplasia in a biopsy
7- race
 Usually this tool is not used in clinics, it’s used for large trials and researches.

IBIS tool
(tyrer-cuzick)
 Website: http://www.ems-trials.org/riskevaluator/
 More accurate than bcrsik tool for individual risk
assessment, thus it’s used in clinic to calculate the risk
of breast caner for your patients.
 IBIS tool include more risk factors than GAIL model
such as previous breast boipsy, BRCA mutations,
detailed family history, mammogram density.

BCSC model
https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm

Penn II model
 Estimate the risk for having BRCA mutations in the
patient and in her family.
 Website:
https://pennmodel2.pmacs.upenn.edu/penn2/

Moderate risk patients
 Including:
1- any patient with 15%-20% life time risk using Tyrer-cuzick model, Gail
or any other models.
2-personal history of treated DCIS or breast CA (the risk increase with
time).
3-LCIS, ADH, ALH diagnosed in young female. (the risk increase with
time).
4- extremely dense breast
 Management:
 1- close observation with mammogram (every 6 months)  consider
MRI screening (especially for patients with dense breast)
 2-hormonal therapy (preferred option) (tamoxifen for 5 years reduce
the risk by half)
 3-consider prophylactic bilateral mastectomy for LCIS if the patient
prefer this option.

High risk patients
 Include the following:
1- any patient with >20% life time risk using Tyrer
model, Gail or any other models.
2- carriers of BRCA mutations
3- 1st degree relative with BRCA mutation
4-radiation therapy to the chest at young age.
5-personal of 1st degree relative with Li-fraumeni
syndrome, cowden syndrome.
6- LCIS or ADH or ALH diagnosed for long duration.
(risk increase with time).

 Management of high risk patients include:
1- close observation with mammogram then MRI (every
6 months).
2-hormonal therapy to reduce the risk (for all patient
with ADH, ALH, LCIS), and for patient with BRCA2
mutation and patients with previous invasive CA or DCIS
with + hormonal receptors.
3-prophylactic bilateral mastectomy and bilateral salpingo-
opherctomy (the best option for patients with BRCA
mutation).
High risk patients

Risk Reduction Strategies
 Lifestyle
- A healthy lifestyle with regular exercise, healthy low fat
diet, maintaining a healthy weight, avoiding smoking, and
avoiding or limiting alcohol are measures that can be
associated with up to 25% reduction in breast cancer risk.
 Medications
- Medications including tamoxifen, raloxifene, exemestane,
and anastrozole have been studied and demonstrated to
have benefit in reducing breast cancer risk.
 Risk Reduction Mastectomy
- for women who have a strong family history of breast
cancer, BRCA carriers.
- bilateral mastectomy.

Signs and symptoms of breast disease
 Any sign or symptom could be a sign or symptom of cancer…
1- mastalgia: cyclic or non-cyclic.
- breast cancer is in the differential diagnosis for breast pain and is the primary diagnosis that
should be ruled out. When pain is due to breast malignancy it is usually noncyclic in nature,
but there can be a cyclic component in premenopausal women.
- management: risk assessment, US or mammogram.
2- discharge: physiologig or pathologic discharge:
- important features: unilateral or bilateral, single duct or multiple ducts, milk discharge or other,
spontaneous or upon stimulation
- physiiologic discharge is defined as: bilateral, non-spontanous, multiple duct milk discharge.
- pathologic discharge: any unilateral, any sigle duct, any spontanous or any discharge other than
milk.
 best next step for pathologic discharge is US & mammogram.
3- skin changes: dimpling, redness, hotness, Peu de’orange:
- sometimes it’s difficult to distinguish mastitis from inflammatory breast CA.
- consider skin biopsy if mastitis did not improve with antibiotics or if mastitis occur in elderly
non-lactating female to rule out inflammatory breast ca.
4- nipple changes: eczema or paget disease of breast, duct ectaisa or cancer.
5- mass

 The following physical findings should raise concern:
- Lump or contour change
- Skin tethering
- Nipple inversion
- Dilated veins
- Ulceration
- Paget disease
- Edema or peau d’orange
 If a palpable lump is found and possesses any of the following features,
breast cancer may be present:
- Hardness
- Irregularity
- Focal nodularity
- Fixation to skin or muscle

Benign breast disease BBD
 The four major categories of BBD lesions are based on the degree of epithelial
proliferation and abnormality as follows: (1) nonproliferative disease (NPD), (2)
proliferative disease without atypia (PDWA), or (3) atypical hyperplasia (AH).
(4) LCIS
 if atypia is present within any benign breast disease , these lesions should be
excised to a free margin. (ALH, ADH, flat epithelial atypia FEA)
 The only type of atypia that is not associated with increase risk of breast CA is
regenerative atypia (AKA reactive atypia).  regenerative atypia seen during
healing process after breast abscess or mastitis or other inflammattory
conditions, no need to excise to free margins.
- we have four types of atypia (atypical cells) including: ALH, ADH, FEA,
regenerative atypia.
- ADH: atypical ductal hyperplasia, ALH: atypical lobular hyperplasia, FEA: flat
epithelial atypia.  these three types need to be excised to free margins.
- regenerative atypia (reactive atypia): no need for surgical excision.

The four categories of benign breast diseases

Concordance & discordance
 Concordance:
- in breast surgery the term concordance indicate that
the radiologic findings are similar to the pathologic
findings (either core needle biopsy or FNA).
 Discordance:
- when the radiologic findings do not meet with the
pathologic findings.
- these terms are commonly used in breast surgery.
- when discordance about breast lesion is present, the
best next step would be excisional biopsy.

1- Nonproliferative disease
- This group of lesions indicates only mildly increased risk of breast
cancer and.
- Include: cysts, fibroadenomas, columnar cell change, and mild ductal
hyperplasia.
- Usually no further intervention is required for nonproliferative diseases.
 Fibroadenoma:
- diagnosis confirmed by core needle biopsy, these lesions do not need to
be surgically excised unless there is discordance with imaging or AH
identified.
- surgical excision is recommended for a fibroadenoma that is
symptomatic, or enlarging, or measures over 2 cm.
- even fibroadenoma increase the risk of breast CA but with a very low
relative risk.

2- proliferative disease without atypia:
- includes moderate/florid ductal hyperplasia, radial scar, complex sclerosing lesion,
sclerosing adenosis, papillary lesions, columnar cell hyperplasia/FEA.
- Radial scar and complex sclerosing lesions: are the same histologically and
distinguished only by their size, with lesions >1 cm termed complex sclerosing lesions.
This is a benign breast lesion that may present as a palpable mass or on breast imaging
and radiologically mimics breast cancer due to its spiculated appearance.
- if atypia is present within a radial scar, these lesions should be excised, also if the lesion is
>1 cm in size, if there is discordance, or the sampling of the lesion is judged to be
inadequate, surgical excision should also be performed.
- Sclerosing adenosis: if concordant with imaging, no further work-up would be needed,
If the imaging is highly suspicious, and the finding of sclerosing adenosis is discordant
with imaging, surgical excision would be advised to rule out malignancy.
- papillary lesions (papilloma): If atypia is present, then surgical excision is required, In
addition, papillary lesions that present as a mass over 1.0 cm in size, or if there is imaging
and pathology discordance, are also managed with surgical excision.
- columnar cell hyperplasia: benign breast condition, if atypia is present with this lesion
it’s called flat epithelial atypia, surgical excision is recommended for FEA diagnosed on
core needle biopsy. As always, surgical excision should be performed in any case of
discordant findings.

3- atypical hyperplasia (AH):
- also known as proliferative disease with atypia, include:
atypical ductal hyperplasia, atypical lobilar hyperplasia,
flat epithelial atypia
- surgical excision to free margins is the standard of care.
- Women with AH have a significantly increased risk of
future breast cancer, estimated as an absolute risk of breast
cancer of 1% to 2% per year.
- women diagnosed with ADH, or ALH 10 years ago will have
> 10% increase risk of breast CA.
- Women diagnosed with ADH or ALH 30 years ago will have
> 30% increase risk of breast CA.

4- Lobular Carcinoma In Situ:
- LCIS most often presents as an incidental finding seen on breast biopsy.
- In 1st january 2018, the AJCC staging system has removed LCIS from breast
cancer list, and consider it as risk factor for malignancy.
- usually No palpable mass or calcifications are identified.
- Studies of mastectomy specimens have shown that LCIS is often multifocal in
nature and can be present in both breasts.
- surgical excision is controversial for LCIS
- management of women with LCIS should include more intensive imaging
surveillance, as well as thorough discussion of risk reduction options,
including prevention medications as well as surgical risk reduction with
prophylactic bilateral mastectomy.
- If LCIS is detected on stereotactic biopsy, wide excision is indicated. Surgical
excision to negative margins is not indicated, In 10-20% of cases, this may
reveal invasive cancer or ductal carcinoma in situ (DCIS).
- Pleomorphic LCIS: variant of LCIS, should be excised to negative margins.
- the current recommendations is to treat PLCIS in a similar manner to DCIS.

Mondor ‘s disease
 rare condition which involves thrombophlebitis of the
superficial veins of the breast and anterior chest wall.
 Patients with this disease often have abrupt onset of
superficial pain, with possible swelling and redness of
a limited area of their anterior chest wall or breast.
There is usually a lump present, which may be
somewhat linear and tender.
 Mondor's disease is self-limiting and generally benign.
A cause is often not identified.
 Management is with warm compresses and pain
relievers, most commonly NSAIDS.

Screening mammogram VS diagnostic
mammogram.
 Screening mammogram: include 2 views (CC, MLO),
done for asymptomatic patients, usually for patients
older than 35 years.
 Diagnostic mammogram: require radiologist to be
present during the mammogram, include more
detailed views (magnification view, compressed view,
extended views) in addition to the CC, MLO views,
done in any symptomatic patient, or if a mass was
found during exam, or if screening mammogram
detect any lesion.

screening
 The American Cancer Society recommendations on breast
cancer screening include:
- Annual mammograms starting at age 40
- Clinical breast examination (CBE) about every 3 years for women
in their 20s and 30s and annually for women 40 and over
- Breast self-examination (BSE)—Women should have baseline
knowledge of how their breasts normally look and feel in order
to report any breast changes to a health care provider right away.
 Diagnostic mammography instead of screening mammography
is used to evaluate patients with breast symptoms or complaints,
such as nipple discharge or a palpable mass. It is also valuable in
the work-up of patients who have had abnormal results on
screening mammography.

How to read mammogram
 First compare the new mammogram images with any old images if the patient have any.
 Second we look for 3 main things:
1-density:
- four categories: A-D.
- category D (very high breast density), is considered a risk factor for breast CA.
- Some centers recommend annual screening breast MRI for females with category D
2- calcifications:
- Malignant-appearing calcifications are usually fine linear branching or fine pleomorphic.
Malignant-appearing calcifications are usually in a grouped, linear, or segmental
distribution.
- Benign calcifications are more likely round, milk of calcium, rim or coarse popcorn-like
calcifications
3- masses.
- The shape of a mass can be described as round, oval, or irregular
- Margins assessment is important because of the infiltrative nature of most breast cancers.
Margins can be described as circumscribed, obscured, microlobulated, indistinct, or
spiculated.
 Suspicous features: microcalcifications, spiculated mass

Spiculated mass with
microcalcification

 DCIS with extensive calcifications involving large areas of the breast.
 In this case due to extensive calcifications mastectomy is preferred over
lumpectomy for the management of DCIS.

 DCIS with diffuse calcifications involving the entire breast.
 In this case due to diffuse calcifications mastectomy is
preferred over lumpectomy for the management of DCIS.

Role of US
 Mammography is the only screening tool for breast cancer that is known to reduce deaths
due to breast cancer through early detection.
 ultrasound and magnetic resonance imaging (MRI) can help supplement mammography
by detecting breast cancers that may not be visible with mammography.
 Ultrasound can be offered as a screening tool for women who:
- are at high risk for breast cancer and unable to undergo an MRI examination. but it does
not replace annual mammography
- are pregnant or should not be exposed to x-rays (which are necessary for a mammogram).
- have increased breast density: when the breasts have a lot of glandular and connective
tissue and not much fatty tissue.
 Ultrasound-guided Breast Biopsy: usually the preferred method to obtain core biopsy
 US is used to differentiate between cystic or solid lesions.
 Cystic lesions should be aspirated under US guidance, if aspirate is bloody send to
cytology.
 If cyst persist after aspiration or recurrent for 2 times or complicated cyst or complex cyst
then excision is advised.
 Pneumocystogram: injecting air into the cyst cavity, the air act as a contrast and makes
the cyst margins more clear and help to identify any solid component.

Ultrasound guidance
 Ultrasound guidance is used in four biopsy procedures:
1- fine needle aspiration (FNA), which uses a very small
needle to extract fluid or cells from the abnormal area.
2- core needle (CN) which uses a large hollow needle to
remove one sample of breast tissue per insertion.
3- vacuum-assisted device (VAD) which uses a vacuum
powered instrument to collect multiple tissue samples
during one needle insertion.
4-wire localization, in which a guide wire is placed into the
suspicious area to help the surgeon locate the lesion for
surgical biopsy.

Types of cysts
 Simple cyst : To be regarded as a simple cyst, a mass must meet 3
criteria:
1- its margins must be circumscribed (i.e., a margin "that is well defined
or sharp, with an abrupt transition between the lesion and surrounding
tissue");
2- it must be anechoic (i.e., "without internal echoes")
3- it must show posterior acoustical enhancement
- Simple cysts are categorized as BIRADS II
 Complicated cyst: similar to simple cyst but contain internal echoes
representing proteinaceous fluid, cholesterol crystals, blood, or other
material. Complicated cysts are categorized as BIRADS II or III
 Complex cyst: cyst that have solid component, the solid component
need biopsy, and this cyst is categorized as BIRADS IV.

Role or MRI
 MRI is used as screening tool in high risk patients or in
patients with dense breast.
 Screening for high risk patients include:
- Mammography and MRI interchangeably every 6
months.
-patients with dense breast (based on mammographic
features, not by physical exam), benefit from screening
MRI in addition to mammogram.

Core needle biopsy
 In case of breast mass the preferred approach to obtain tissue is with
percutaneous core needle breast biopsy.
 Percutaneous vacuum-assisted large-gauge core-needle biopsy (VACNB) with
image guidance is the recommended diagnostic approach for newly diagnosed
breast tumors.
 Generally, this is an image-guided biopsy performed under ultrasound,
stereotactic, or magnetic resonance imaging guidance. In the uncommon
situation of a suspicious palpable abnormality and negative imaging findings,
freehand core needle biopsy can be performed.
 Core needle biopsy give the [athologist the ability to determine the hormonal
status of the breast cancer.
 the pathology findings must be plausible to explain the imaging features of the
lesion. (concordance)
 If discordant, such as when the imaging suggests a “suspicious finding”
classified as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 but
the pathology is benign, Surgical excision of the lesion is the recommended
approach to manage discordant breast Lesions.

 benign lesions diagnosed on core needle biopsy that
are shown to have an increased risk that cancer may be
present within the lesion but can only be diagnosed
accurately with complete surgical excision (so-called
“borderline” or “high-risk” lesions). In these
situations where adequate diagnosis is best made with
complete surgical excision of the lesion.
 The term “high risk lesion” has also been used to
describe breast lesions that confer a long-term
increased risk of breast cancer (generally atypical
ductal hyperplasia [ADH], atypical lobular hyperplasia
[ALH], and lobular carcinoma in situ [LCIS]).

Fine Needle Aspiration Biopsy
 The diagnostic accuracy of FNA biopsy of breast
masses approximates 80%.
 False-negative results occur in approximately 15% of
cases and thus a lesion that is suspicious clinically or
by imaging must be further investigated with core
biopsy.
 Suspicious axillary lymph nodes may also be assessed
with FNA.
 Core biopsy is the preferred method of evaluating
suspicious solid mass.

Needle Localization Biopsy
 Nonpalpable breast mass makes a challenge for surgeons in order to identify this mass during
operation and excision of this mass with free margins.
 This challenge has led to the development of several methods for preoperative localization of
nonpalpable lesions.
 Radiologically guided, invasive preoperative localization of nonpalpable lesions is a safe, simple, and
established procedure that allows for accurate and expeditious biopsy or excision.
 wire localization:
- This technique utilizes a flexible, hooked wire within the localizing needle.
- The wire may be placed in most circumstances using mammography or ultrasound guidance, although
MR-guided wire localization can also be performed.
- Once the specimen is removed, it should be oriented for the pathologist. A variety of orienting
techniques can be used, including sutures or indelible ink (paint). The specimen is then sent for
specimen radiograph to conclusively confirm full excision of the suspicious/malignant lesion.
 Radioactive Seed Localization:
- Radioactive seed localization (RSL) is an alternative for guiding surgical excision of nonpalpable breast
lesions
- iodine-125 and palladium-103 seeds between 200 and 300 μCi/seed are implanted into the breast lesion
using a standard 18-gauge needle. The seeds can be implanted using mammography or ultrasound
guidance, but seeds are not MRI compatible.

Vacuum-assisted breast biopsy
 vacuum-assisted device (VAD): vacuum pressure is
used to pull tissue from the breast through the needle
into the sampling chamber. Without withdrawing and
reinserting the needle, it rotates positions and collects
additional samples. Typically, eight to 10 samples of
tissue are collected from around the lesion.
 Obtain tissue sample as core needle biopsy.

Punch biopsy (skin biopsy)
 diagnosis of inflammatory breast cancer is made largely
clinically, histologic confirmation of cancer cells within the
dermal lymphatics is pathognomonic for inflammatory breast
cancer.
 In patients who present with skin changes, including erythema
and/or peau d’orange, a (3- to 5-mm) punch biopsy can be
performed in the office using local anesthesia.
 The biopsy should be full thickness through the most suspicious
area.
 Most inflammatory breast cancers do not present with a palpable
mass, but if present, a core biopsy can then be obtained through
the punch biopsy site to provide more tissue for receptor assays.

-histologic subtypes
-genomic subtypes
-HER2/neu status
DCIS & managment

 Breast cancer most commonly develops in cells from
the lining of milk ducts and the lobules that supply the
ducts with milk. Cancers developing from the ducts
are known as ductal carcinomas, while those
developing from lobules are known as lobular
carcinomas. In addition, there are more than 18 other
sub-types of breast cancer.

Types of breast CA
1- Infiltrating ductal carcinoma (invasive ductal not otherwise specific) is the most
commonly diagnosed breast tumor and has a tendency to metastasize via lymphatics;
this lesion accounts for 75% of breast cancers
2- Infiltrating lobular carcinoma accounts for fewer than 15% of invasive breast cancers
3- Medullary carcinoma accounts for about 5% of cases and generally occurs in younger
women
4- Mucinous (colloid) carcinoma is seen in fewer than 5% of invasive breast cancer cases
5- Tubular carcinoma of the breast accounts for 1-2% of all breast cancers
6- Papillary carcinoma is usually seen in women older than 60 years and accounts for
approximately 1-2% of all breast cancers
7- Metaplastic breast cancer accounts for fewer than 1% of breast cancer cases, tends to occur
in older women (average age of onset in the sixth decade), and has a higher incidence in
blacks
8- Mammary Paget disease accounts for 1-4% of all breast cancers and has a peak incidence
in the sixth decade of life (mean age, 57 years)
9- inflammatory breast CA

Infiltrating ductal carcinoma &
infiltrating lobular carcinoma
 Infiltrating ductal carcinoma is the most commonly
diagnosed breast tumor and has a tendency to
metastasize via lymphatic vessels. Like ductal
carcinoma, infiltrating lobular carcinoma typically
metastasizes to axillary lymph nodes first. However, it
also has a tendency to be more multifocal.
Nevertheless, its prognosis is comparable to that of
ductal carcinoma.

Infiltrating ductal CA
 Also known as invasive ductal not otherwise specific.
 Many subtypes: pleomorphic carcinoma, carcinoma with
osteoclast-like stromal giant cells, carcinoma with
choriocarcinomatous features, and carcinoma with
melanotic features, Mucinous, papillary, cribriform, and
tubular carcinomas.
 The most common type of breast CA
 The prognosis of IDC depends, in part, on its histological
subtype: Mucinous, papillary, cribriform, and tubular
carcinomas have longer survival, and lower recurrence
rates. The prognosis of the most common form of IDC,
called "IDC Not Otherwise Specified", is intermediate.

mucinous carcinoma & tubular carcinoma:
- Mucinous (colloid) carcinoma is another rare histologic
type, seen in fewer than 5% of invasive breast cancer cases.
- Most cases are ER- and PR-positive, but HER2
overexpression is rare. (luminal A).
- have an excellent prognosis, with better than 80% 10 year
survival.
- has a low incidence of lymph node involvement and a very
high overall survival rate.
- Because of the favorable prognosis, patients weith these
cancers are often treated with only breast-conserving
surgery and local radiation therapy.

medullary carcinomas
 Medullary carcinoma is relatively uncommon (5%) and
generally occurs in younger women.
 ER negative, high tumor grade, and high proliferative
rates.

Papillary carcinoma
 This form of breast cancer is usually seen in women
older than 60 years and accounts for approximately 1-
2% of all breast cancers.
 Papillary carcinomas are centrally located in the breast
and can present as bloody nipple discharge. They are
strongly ER- and PR-positive.
 There are 2 common types: cystic (noninvasive form –
good prognosis) and micropapillary ductal carcinoma
(invasive form – intermediate prognosis).

Metaplastic breast cancer
 Metaplastic breast cancer (MBC) accounts for fewer than 1% of breast
cancer cases.
 It is characterized by a combination of adenocarcinoma plus
mesenchymal and epithelial components.
 Compared with infiltrating ductal carcinoma, MBC tumors are larger,
faster-growing, commonly node-negative, and typically negative for
ER, PR, and HER2. (bad prognosis)
 A wide variety of histologic patterns includes the following:
1- Spindle-cell carcinoma
2- Carcinosarcoma
3- Squamous cell carcinoma of ductal origin
4- Adenosquamous carcinoma
5- Carcinoma with pseudosarcomatous metaplasia
6- Matrix-producing carcinoma

Mammary Paget disease
 Mammary Paget disease is relatively rare, accounting
for 1-4% of all breast cancers.
 This adenocarcinoma is localized within the epidermis
of the nipple-areola complex
 Lesions are predominantly unilateral, developing
insidiously as a scaly, fissured, oozing, or erythematous
nipple-areola complex.
 In situ or invasive breast cancer is found in
approximately 85% of patients with Paget disease.
 Punch biopsy of the skin & nipple is recommended.

Inflammatory breast cancer
 Inflammatory breast cancer is one of the most aggressive types of breast cancer that can
occur in women of any age (and, extremely rarely, in men).
 IBC makes up only a small percentage of breast cancer cases (1-6%)
 It is called inflammatory because it frequently presents with symptoms resembling an
inflammation.
 Usually triple negative.
 present with very variable signs and symptoms, frequently without detectable mass and
therefore is often not detected by mammography or ultrasound.
 Typical presentation is rapid swelling, sometimes associated by skin changes (peau
d'orange), and nipple retraction. Other symptoms include rapid increase in breast size,
redness, persistent itching, skin hot to touch.
 IBC often initially resembles mastitis.
 Suspect IBC in any non-lactating female with mastitis not responding to antibiotic
treatment.
 The only reliable method of diagnosis is full-thickness skin biopsy  (cancer cells in the
subdermal lymphatics on skin biopsy).
 At least considerd stage IIIB, stage IIIC if node involved, stage IV if metastasis.
 The standard treatment for inflammatory breast cancer is:
Neo-adjuvant systemic therapy + MRM + ALND + adjuvant chemo-radiotherapy.

Phylloides tumors
 Phylloides tumors are a fibro-epithelial tumor composed of an epithelial and a cellular
stromal component.
 They account for less than 1% of all breast neoplasms.
 Occurrence is most common between the ages of 40 and 50.
 These tumors are very fast-growing, and can increase in size in just a few weeks
 They may be considered benign, borderline, or malignant depending on histologic
features including stromal cellularity, infiltration at the tumor's edge, and mitotic
activity.
 Malignant phyllodes tumours behave like sarcomas and can develop blood-borne
metastases.
 The common treatment for phyllodes is wide local excision. Other than surgery, there is
no cure for phyllodes, as chemotherapy and radiation therapy are not effective.
 The risk of developing local recurrence or metastases is related to the histologic grade.
 Despite wide excision, a very high percentage of surgeries yielded incomplete excision
margins that required revision surgery.
 Radiation treatment after breast-conserving surgery with negative margins may
significantly reduce the local recurrence rate for borderline and malignant tumors

Genomic subtypes of Breast CA
 Genomic profiling has demonstrated the presence of
discrete breast tumor subtypes with distinct natural
histories and clinical behavior.
 these subtypes generally align with the presence or absence
of estrogen receptor (ER), progesterone receptor (PR), and
human epidermal growth factor receptor 2 (HER2).
 Thers is 4 main breast tumor subtypes, with distinct
genetic and epigenetic aberrations:
1- Luminal A (the least aggressive) (ER+/PR+/HER2-)
2- Luminal B (triple positive)
3-HER2-positive (ER-/PR-/HER+)
4- Basal-like (the most aggressive) (triple negative)

HER2
 In the past, HER2 overexpression was associated with a more
aggressive tumor phenotype and a worse prognosis (higher
recurrence rate and increased mortality), independent of other
clinical features (eg, age, stage, and tumor grade), especially in
patients who did not receive adjuvant chemotherapy.
 Prognosis has improved with the routine use of HER2-targeted
therapies, which consist of the following:
- Trastuzumab – Monoclonal antibody
- Pertuzumab – Monoclonal antibody
- Lapatinib – A small-molecule oral tyrosine kinase inhibitor
- Neratinib – A small-molecule oral tyrosine kinase inhibitor
- Ado-trastuzumab emtansine – An antibody-drug conjugate
directed specifically to the HER2 receptor

HER2 testing
 Several methods for HER2 testing have been developed.
 Initial validated immunohistochemistry (IHC) tests include:(HercepTest,
Dako, Glostrup, Denmark).
 The scoring method for HER2 expression is based on the cell membrane
staining pattern and is as follows:
 3+ : Positive for HER2 protein expression.
 2+ : Equivocal for HER2 protein expression.
 1+ : Weak or incomplete membrane staining in any tumor cells
 0 : Negative for HER2 protein expression; no staining.
 equivocal IHC results (+2) should undergo validation with a HER2 gene
amplification method, such as fluorescence in situ hybridization (FISH).
 Treatment with trastuzumab is recommended for +3 and +2 (after validation
with FISH).
 Newer methods for establishing HER2 status, including reverse transcriptase–
polymerase chain reaction (RT-PCR) and chromogenic in situ hybridization
(CISH), have been developed.

prognosis
 Breast cancer prognostic factors include the following:
- Axillary lymph node status
- Tumor size
- Lymphatic/vascular invasion
- Patient age
- Histologic grade
- Histologic subtypes (eg, tubular, mucinous [colloid], or papillary)
- Response to neoadjuvant therapy
- ER/PR status
- HER2 gene amplification or overexpression
 involvement of the lymph nodes in the axilla is an indication of the likelihood that the breast cancer
has spread to other organs. Survival and recurrence are independent of level of involvement but are
directly related to the number of involved nodes.
 Patients with node-negative disease have an overall 10-year survival rate of 70% and a 5-year
recurrence rate of 19%.
 Patients with lymph nodes that are positive for cancer, the recurrence rates at 5 years are as follows:
- One to three positive nodes – 30-40%
- Four to nine positive nodes – 44-70%
- ≥10 positive nodes – 72-82%

DCIS
 Ductal carcinoma in situ: cancer but have not yet invade the basement
membrane.
 Usually no palpable mass can be detected.
 Present as linear or branching calcifications on mammogram.
 DCIS is divided into comedo (ie, cribriform, micropapillary, and solid) and
noncomedo subtypes, a division that provides additional prognostic
information on the likelihood of progression or local recurrence.
 Generally, the prognosis is worse for comedo DCIS than for noncomedo DCIS.
 There is 20% risk of having invasive cancer with DCIS.
 Management depends on:
1- Van-nuys score
2-receptor status: if estrogen receptor + (tamoxifin, raloxifine, aromatase
inhibitors), if HER2+ (trastuzumab)
3-axillary lymph node status (from it’s definition it should be in situ but
remember there is 20% chance to have invasive cancer with DCIS so remember
to examine L.Ns).

Management of DCIS
 Van-nuys score is calculated after doing lumpectomy and sending
the lesion to histopathology where grade and margins are identified
and measured and pure DCIS is identified.
 (lumpectomy alone) or (lumpectomy and radiotherapy) or
(mastectomy): depends on Van-nuys score:
- If V-N 4-6 lumpectomy alone.
- If V-N 7-9 lumpectomy and radiotherapy.
- If V-N 10-12 mastectomy. (SLNB with mastectomy)
 Hormonal and trastuzumab therapy: according to receptor status.
 SLNB must be done if:
1- mastectomy to be done 2- lumpectomy at the upper lateral
quadrant 3-breast reconstruction surgery 4- large DCIS >5cm

DCIS
 Given the 20% rate of invasive cancer evident on
histologic assessment after excision of patients
diagnosed on core as DCIS, sentinel node biopsy is
often combined with mastectomy. (mastery of surgery)
 SLNB in DCIS: limit the procedure (SLNB) to those
who will undergo a mastectomy or immediate
reconstruction or a wide local excision involving
the upper outer quadrant. This is because of the
difficulty of performing a SLN procedure after these
surgical procedures as they may disrupt the lymphatic
pathways toward the axilla. (NCBI)

 Mastectomy or surgery in the upper lateral quadrant or breast reconstruction surgery
might damage the lymphatic flow to the axilla which will make SLNB difficult in the
future, therefore in these cases SLNB should be done at the time of surgery even if initial
assessment of axillary Lymph nodes are not suspicious.
- if axillary L.N are palpable by exam or enlarged by US, then FNA should be taken to
confirm involvement with CA and consider the presence of invasive cancer together with
DCIS.
 Special cases:
1- if DCIS occur in patient with BRCA mutation then the best option would be bilateral
mastectomy with SLND with hormonal therapy in case of BRCA2 mutation or if receptor
+ in DCIS.
2-if DCIS occur with extensive micro-calcifications (extensive means involving large are of
the breast) then mastectomy is preferred over lumpectomy.
3- if DCIS occur with LCIS then hormonal therapy should be given regardless of hormonal
status.
4- if negative margins cannot be achieved after two wide local excisions then mastectomy is
recommended.
5- if there is contraindications to radiotherapy then mastectomy is recommended
6- multifocal DCIS require mastectoomy.
7- DCIS in males: males have small breast so mastectomy is recommended

Staging
 There are four different types of staging:
1- Clinical Staging determines how much cancer there is based on the physical
examination, imaging tests, and biopsies of affected areas.
2- Pathologic Staging can only be determined from individual patients who have
had surgery to remove a tumor or explore the extent of the cancer. Pathologic
staging combines the results of both the clinical staging (physical exam,
imaging test) with surgical results.
3- Post-Therapy or Post-Neoadjuvant Therapy Staging determines how much
cancer remains after a patient is first treated with systemic (chemotherapy or
hormone therapy) and/or radiation therapy prior to their surgery or where no
surgery is performed. This can be assessed by clinical staging guidelines and/or
pathologic staging guidelines.
4- Restaging is used to determine the extent of the disease if a cancer comes back
after treatment. Restaging helps determine the and the best treatment options
for cancer that has returned.

Staging of Breast CA
 Based on: TNM system & genomic subtype.
 The 5-year survival rates are highly correlated with
tumor stage, as follows:
- Stage 0: 99-100%
- Stage I: 95-100%
- Stage II: 86%
- Stage III: 57%
- Stage IV: 20%

Staging
-T-
 Tumor size definitions are as follows:
- Tx: Primary tumor cannot be assessed - T0 – No evidence of primary tumor
- Tis: DCIS or LCIS (the old classification)
- Tis: Paget disease of the nipple with no tumor (Paget disease associated with a tumor is
classified according to the size of the tumor)
 T1: Tumor ≤2 cm in greatest diameter
- T1mic – Microinvasion ≤0.1 cm in greatest diameter
- T1a – Tumor >0.1 but not >0.5 cm in greatest diameter
- T1b – Tumor >0.5 but not >1 cm in greatest diameter
- T1c – Tumor >1 cm but not >2 cm in greatest diameter
 T2: Tumor >2 cm but not >5 cm in greatest diameter
 T3: Tumor >5 cm in greatest diameter
 T4: Tumor of any size, with direct extension to (a) the chest wall or (b) skin only, as
described below
- T4a – Extension to the chest wall, not including the pectoralis
- T4b – Edema (including peau d’orange) or ulceration of the skin of the breast or satellite
skin nodules confined to the same breast
- T4c – Both T4a and T4b
- T4d – Inflammatory disease

Staging
-N-
 Clinical regional lymph node definitions are as follows:
 Nx – Regional lymph nodes cannot be assessed (eg, previously
removed)
 N0 – No regional lymph node metastasis
 N1 – Metastasis in movable ipsilateral axillary lymph node(s)
 N2:
- N2a – Metastasis in fixed ipsilateral axillary lymph nodes to one
another or to other structures
- N2b – Metastasis only in clinically apparent ipsilateral internal
mammary nodes and in the absence of clinically evident axillary
lymph nodes
 N3:
- N3a – Metastasis in ipsilateral infraclavicular lymph node(s)
- N3b – Metastasis in ipsilateral internal mammary lymph node(s) and
axillary lymph node(s)
- N3c – Metastasis in ipsilateral supraclavicular lymph node(s)

Staging
-M-
 Metastases are defined as follows:
- Mx: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
 Screening for metastasis is not routinely done for every patient.
 Screening for metastasis is done in the case of:
1- symptomatic patient (bone pain, pathologic fracture, new onset seizures, jaundice, bowel obstruction,
significant weight loss, hemoptesis, etc…)
2- patient with locally advanced disease (T3, N1, N2). Even if the patient is asymptomatic.
 Bone scan and CT of the chest/abdomen/pelvis are recommended for patients with clinical or
pathologic stage IIIA-C disease
 Functional imaging with fluorodeoxyglucose (18 F) positron emission tomography (FDG-PET) may
offer improved diagnostic accuracy over CT alone
 In early operable breast cancer (Tl to 2, N0 to 1), there is no current evidence to support routine
screening for metastatic disease in asymptomatic women.
 Patients with symptoms suggestive of metastases at a particular site require appropriate investigation.
 The incidence of asymptomatic metastases increases as the T and N stage increases.
 patients with more advanced but operable disease (T3 and multiples N1 nodes or N2 disease clinically
or on imaging) should be considered for investigations to exclude distant metastases.

Molecular profiling assays
-The Onco type Dx assay
- MammaPrint assay
 These assay are used in case of: early stage hormonal positive breast
cancer to estimate the risk of distant recurrence.
 The goal of these assay is to decide if the patient need chemotherapy or
not in order to decrease the risk of distant recurrence.
- The Onco type Dx assay : genetic test that measures the activity of 21
genes to determine the 5- to 10-year relapse risk
- MammaPrint assay: genetic test that measures the activity of 70 genes to
determine the 5- to 10-year relapse risk.
Onco type Dx:
- Recurrence score (RS) can be calculated that correlates with the
likelihood of distant recurrence at 10 years as follows:
 RS < 18, low risk (hormonal therapy alone)
 RS 18-30, intermediate risk (hormonal and chemotherapy in young
females <50 years), (hormonal therapy alone if >50 years).
 RS >30, high risk (hormonal and chemotherapy).

Treatment of
invasive breast cancer
1- Neoadjuvant therapy.
2- Breast surgery (WLE “lumpectomy” AKA (breast
conserving surgery), simple mastectomy, MRM).
3- Axilla surgery (SLND or ALND).
4- Adjuvant therapy (chemotherapy, radiotherapy,
hormonal therapy).

Adjuvant chemotherapy
&
Adjuvant endocrine therapy

Neoadjuvant therapy
 Neoadjuvant therapy refers to the systemic treatment of breast cancer prior to definitive surgical therapy.
 neoadjuvant treatment has taken the form of neoadjuvant chemotherapy, although there is increasing interest in
expanding the role of neoadjuvant endocrine therapy in certain subsets of patients.
 The most important clinical goals remain to improve disease-free and overall survival and to reduce the size of the
tumor so as to facilitate more effective surgery.
 Any patient who is a candidate for adjuvant systemic therapy can be considered for neoadjuvant treatment.
 If no active cancer cells are present in a tissue extracted from the tumor site after neoadjuvant therapy, physicians
classify a case as “pathologic complete response” or "pCR.“
 Neoadjuvant chemotherapy is indicated in the following:
1- all patients with inflammatory breast carcinoma
2- ipsilateral supraclavicular L.N involvment.
3- bulky axillary adenopathy.
4- extension to the skin or chest wall
5- large (>5 cm) primary tumor.
6- ER-negative disease
7- HER2-positive disease
 Many regimen available most commonly used is: TAC: Docetaxel (Taxotere) 75 mg/m2 IV on day 1 plus doxorubicin
(Adriamycin) 50 mg/m2 IV on day 1 plus cyclophosphamide 500 mg/m2 IV on day 1 every 3 wk for six cycles.
 For HER2-positive tumors, the following neoadjuvant regimen is administered every 3 wk for three to six cycles:
- Pertuzumab (Perjeta): 840 mg IV infusion over 60 min, then 420 mg IV infusion over 30-60 min plus trastuzumab: 8
mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min plus Docetaxel: 75 mg/m² IV
infusion initially; may increase to 100 mg/m² IV infusion if initial dose is well tolerated

Breast conserving surgery BCS
Vs
Mastectomy

Breast surgery
lumpectomy vs mastectomy
 lumpectomy alone is wrong answer when talking about invasive cancer, always
lumpectomy is combined with radiotherapy to decrease local recurrence (local
control).
 mastectomy is indicated for the following:
1- T3 or T4 tumor ***
2-N2 or more
3-inflammatory CA
4-if there is contraindications to radiotherapy (pregnancy, active connective tissue
disease, previous radiation to the chest, P53 miutaion “li-fraumini syndrome).
5-multifocal lesions
6- large tumor size relative to breast size in T1 or T2
7-diffue or extensive calcifications
8- positive margins after 2 WLE
9- patients with BRCA mutation.
- Otherwise lumpectomy + radiotherapy is indicated.

BREAST-CONSERVING SURGERY
 Tumor size:
- Clinical assessment of tumor size usually overestimates tumor size
- It is the balance between tumor size as assessed by imaging and breast volume that determines whether a
patient is suitable for BCT.
- Patients with tumors measuring clinically larger than 4 cm can be treated by BCT if the patient has
large breasts.
- Conversely, in a patient with small breasts, excision of even a 1-cm tumor may produce an unacceptable
cosmetic result.
- Options for patients with tumors considered too large relative to the size of the breast for BCT include
neoadjuvant systemic therapy to shrink the tumor or an oncoplastic procedure, involving either
transfer of tissue into the breast or surgery to reduce the size of the breast usually combined with
synchronous contralateral reduction.
 patients with multiple tumors in the same breast:
- if the cancers can be excised to clear margins even if they are far apart and a satisfactory cosmetic
outcome produced, then BCT is feasible.
 Previous contraindications no longer considered as contraindications for BCT; These include:
1- young age (<35 to 39 years),
2- the presence of an extensive in situ component associated with an invasive tumor,
3- grade 3 histology
4- widespread lymphatic/vascular invasion (LVI).

INDICATIONS AND CONTRAINDICATIONS TO
BREAST CONSERVING TREATMENT

Axillary surgery
 The presence or absence of axillary lymph node
involvement is an important predictor of survival in
patients with breast cancer.
 Assessment of Lymph node:
- initial assessment by physical exam and US followed
by FNA for any suspicious Lymph nodes.

SLNB
 SLNB: used to evaluate axillary lymph nodes in patient with operable breast
cancer (T1, T2) and clinically node-negative.
 SLNB relies on the principle that the breast drains predictably and
preferentially to the axilla, and that within the axilla, there exist guardian or
“sentinel” nodes that are the first to receive metastatic tumor cells in the case of
dissemination beyond the breast mound.
 SLNB is considered the standard of care for axillary staging in patients with
clinically node-negative breast cancer.
 SLNB is indicated for patients with nonmetastatic, T1-T2 breast cancer and no
palpable lymphadenopathy.
 It is contraindicated in patients with inflammatory breast cancer or clinically
palpable nodal disease regardless of response to neoadjuvant chemotherapy
(NACT).

SLNB
 Neither previous augmentation nor prior mammoplasty is a contraindication to SLNB. Also SLNB
can still be performed in patients who have undergone previous SLNB.
 Tracers used in SLNB: Radiocolloid, isosulfan blue or methylene blue.
 In pregnant women, SLNB has usually been performed with radiocolloid only.
 dual agent mapping is especially important for those patients who have undergone neoadjuvant
systemic therapy, patients who have undergone prior breast or axillary surgery, and patients with
recurrent breast cancer.
 Prior to injection of isosulfan blue (which is the preferred dye), the patient is administered a
glucocorticoid, diphenhydramine (Benadryl), and famotidine as a prophylactic measure to minimize
the severity of any allergic response the patient might have to the blue dye.
 Tracer can be injected into the subareolar region, intradermally into the skin overlying the tumor,
or around the tumor.
 Subareolar injection of tracer has advantages over peritumoral injection in patients with multisite
or nonpalpable cancers.
 The breast is then massaged for 5 minutes to facilitate movement through the lymphatic channels to
the sentinel node(s).

SLNB
 The density of lymphatics is greater in the skin than in
breast parenchyma, so uptake in the axillary nodes is
greater with intradermal injection than other sites.
 Detection rate with blue dye of 90%, compared with
98% for radioactive colloid. They recommended using
both modalities to enhance sentinel lymph node
detection.
 SLNB results reported as: (negative, isolated tumor
cells, micrometastasis, macrometastasis).

SLNB
 anatomical studies show the majority have two draining lymphatics ending at
either the pectoral node, situated medially behind the pectoralis major muscle,
or a second node laterally situated just above the axillary tail, then the average
number of sentinel nodes a surgeon should be removing to limit the false
negative rate is between two and three, and should include nodes at these two
locations.
 When using dye, between 2.0 and 7.5 mL of isosulfan blue, patent blue V, or
methylene blue is injected just before the skin is prepared for surgery.
 The two classical sites for sentinel nodes are in the subpectoral region—low
and medial—and in the low lateral axilla just above the axillary tail of the
breast. Two or more sentinel nodes are usually evident, and all the nodes
identified with the handheld probe containing significant isotope (10% or more
of the radioactivity of the hottest node) or stained blue should be removed and
sent for histologic evaluation.

SLNB
 A small (∼2 to 3 cm) transverse incision is made just
below the axillary hairline, over the transcutaneous
“hot spot” Dissection through the subcutaneous tissue
is carried out using electrocautery and the
clavipectoral fascia is opened.
 Sentinel node(s) are defined as those nodes that are
either “hot” or blue. Nodes that are <10% of the
highest ex vivo count with the gamma probe are not
considered sentinel nodes.

SLNB
 If the sentinel lymph nodes are negative, no further axillary surgery is needed.
If metastases are identified, the size of metastasis may dictate the need for
additional surgery.
 Nodal metastasis is reported as isolated tumor cells (<0.2 mm),
micrometastasis (0.2 to 2 mm), or macrometastasis (>2 mm).
 Patients with isolated tumor cells require no further axillary surgery as this is
considered N0(i+) disease
 patients with either micrometastases or macrometastases in one or two lymph
nodes do not require additional axillary surgery if the patient received whole
breast irradiation, as long as extranodal extension is absent.
 Patients who did not receive whole breast radiation who have either
micrometastases or macrometastases should undergo completion ALND.
 SLNB have fewer complications compared to ALND; which include:
anaphylaxis after receiving blue dye for lymphatic mapping (0.1%), axillary
wound infection (1%), axillary seroma (7.1%), axillary hematoma (1.4%),
axillary paresthesias (8.6%), decreased upper extremity range of motion
(3.8%), and upper extremity lymphedema (6.9%).

ALND
 ALND offered to the following patients:
- Large or locally advanced invasive breast cancer (tumor size T3/T4).
- Inflammatory breast cancer.
- Failure to obtain SLNB
- Pregnant women because they cannot undergo SLNB. ***
- Any patient with involved nodes (micrometastasis or macrometastasis) by SLNB who did not
receive whole breast radiotherapy.
- Any patient underwent Neoadjuvant therapy (even if L.N become clinically negative after NACT).
(SLNB has false-negative rates of >10% in patients with N1 disease prior to NACT, indicating that SLNB
alone is not a reliable alternative to ALND in axillary staging after NACT.) mastery of surgery
 axillary dissection: Some surgeons perform a level I/II dissection, others remove levels I and II,
and some remove all nodes to level III routinely.
 Axillary lymph node involvement usually start at level I & II, although in 5% of cases there is
what so called (skip metastasis) in which the initial lymph node level involved is level III
*** isosulfan blue or methylene blue dye is contraindicated for SLNB in pregnancy; radiolabeled sulfur colloid
appears to be safe.

•Care is taken to identify and preserve the medial pectoral nerve and vessels that pass
into the lateral border of the pectoralis minor muscle from the pectoralis major: these
innervate both and supply the pectoralis minor and the lower lateral third of the
pectoralis major muscle

-chemotherapy
-radiotherapy
-endocrine therapy

Adjuvant chemotherapy
 3 generations of chemotherapy regimens are available.
 The 3rd generations are more affective and more clinically used.
 Indications:
1- any inflammatory CA
2- any advanced CA
3- early stage CA in patients with Onco type Dx Recurrence score (RS)
=>18 in young females or (RS) =>25 in older females.
 Third-generation regimens include both taxanes and anthracyclines.
Most commonly used regimens include:
- AC-paclitaxel: Doxorubicin 60 mg/m2 IV plus cyclophosphamide 600 mg/m2 IV on day 1 every
3 wk for four cycles, followed by paclitaxel 80 mg/m2 by 1-h IV infusion weekly for 12 wk.
or
- TAC: Docetaxel 75 mg/m2 IV plus doxorubicin 500 mg/m2 IV plus cyclophosphamide 500
mg/m2 IV on day 1 every 3 wk for six cycles.
 Important to perform echochariography for patients before receiving
trastuzumab or doxorubicin because both of them are cardiotoxic.

Radiotherapy “RT”
 Include:
- Whole-breast RT alone.
- Whole-breast RT with boost to the tumor bed.
- Whole-breast RT with boost to the tumor bed + RT to the infraclavicular and
supraclavicular areas.
- Whole-breast RT with boost to the tumor bed + RT to the infraclavicular and
supraclavicular areas + RT to internal mammary nodes.
- Chest wall RT +- RT to the infraclavicular and supraclavicular areas +- RT to internal
mammary nodes
 RT usually follow chemotherapy if chemotherapy is indicated.
 Indications for RT:
- After any lumpectomy for invasive cancer.
- After mastectomy for T3, T4, N2, N3, N4 tumors. (recent guidelines include even
N1).
- Any inflammatory breast CA
- DCIS with Van-Nuys score => 7
- High risk patients
- Inability to gain free margins after mastectomy.

Adjuvant Endocrine Therapy, ER/PR+
 Patients with invasive breast cancer that is estrogen receptor (ER) or
progesterone receptor (PR)–positive should be considered for adjuvant
endocrine therapy. Options for endocrine therapy in breast cancer patients
include the following:
- Selective Estrogen receptor modifiers(SERMs): Tamoxifen /raloxifine
- Aromatase inhibitors (AIs): Nonsteroidal (anastrozole, letrozole) and steroidal
AIs (exemestane)
- Luteinizing hormone–releasing hormone (LHRH) analogues
- Oophorectomy may produce additional benefit
 Selection of agents depends on menopausal status and concern about side-
effect profile (eg, thrombosis with tamoxifen, bone loss with AIs).
 AIs are effective for postmenopausal women.

Adjuvant Endocrine therapy
 Regimens for premenopausal patients
- Tamoxifen 20 mg PO daily for 5 y
or
 Tamoxifen 20 mg PO daily for 2-5 y, followed by an AI for a
total of up to 10 y of endocrine therapy; this regimen is
typically used for patients who are premenopausal at
diagnosis and become postmenopausal during therapy; it
has been shown to be more effective than a 5-y course of
tamoxifen
 Ovarian suppression with LHRH analogues, added to
tamoxifen or an AI, is associated with a modest effect; this
approach is being evaluated in ongoing trials

Adjuvant Endocrine therapy
 Regimens for postmenopausal patients:
- Tamoxifen 20 mg PO daily for 5 y
or
- AIs for 5y, either alone or sequentially after 2-5 y of
tamoxifen: anastrozole 1 mg PO daily or letrozole 2.5
mg PO daily or exemestane 25 mg PO daily

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