BREAST PATHOLOGY

Fibrocystic Changes, Invasive Ductal Carcinoma of The Breast, NST; N85/86

Fibroadenoma of The Breast; N8
Common clinical
presentations of breast
disease
NORMAL BREAST ANATOMY CROSS-SECTION

1. Chest wall
2. Pectoralis muscles
3. Lobules
4. Nipple
5. Areola
6. Milk duct
7. Fatty tissue
8. Skin
Normal breast: there are 15 to 20
sections (lobes) inside a woman's
breast. Each lobe is made of many
smaller sections (lobules).
Lobules have groups of tiny glands that can make milk
(acini). Successive branching of the large ducts
eventually leads to the terminal duct lobular unit
(TDLU).
Each acinus and duct has an inner epithelial cell lining
and the supporting myoepithelial or basal cell layer.
Lifecycle changes.
A, Mammograms in young women are typically "dense" or white in appearance. In this setting, mass-forming
lesions or calcifications can be difficult to detect.
B, The density of a young woman's breast is due to the predominance of fibrous interlobular stroma and the
paucity of adipose tissue (normally radiolucent or black).
C, During pregnancy, branching of terminal ducts results in more numerous TDLUs, and the number of acini
per TDLU increases.
D, With increasing age, the TDLUs decrease in size and number, and the interlobular stroma is replaced by
adipose tissue. An older woman's breast typically consists of small ducts and atrophic lobules in adipose
tissue.
E, Mammograms become more radiolucent (darker) with age owing to the increase in adipose tissue. Radio-
dense mass-forming lesions, and calcifications become easier to detect.
Frequency of benign and
malignant breast lesions
diagnosed after biopsy by clinical
presentation and age

It is different in PNG! Cancers are found

in younger woman! In the group of 43
patients with histologically confirmed
diagnoses of breast carcinoma (operated
in M.H. from 16/07/2015 to
05/01/2017), an average age was 45
years of life, the youngest patient was
27, and 23/36 (64%) were 45 year-old or
younger (the age of 7 patients was
unknown).
 Representation of the findings
in a series of women seeking
evaluation of apparent breast
"lumps”.

The average size of an invasive carcinoma

detected by palpation is 2.4 cm,
by mammography - 1.1 cm
Fine Needle Aspiration (FNA)
BENIGN EPITHELIAL LESIONS

1. Nonproliferative breast changes (fibrocystic changes):

- cystic change, often with apocrine metaplasia;
- fibrosis;
- adenosis.

2. Proliferative breast disease without atypia:

- epithelial hyperplasia;
- sclerosing adenosis;
- complex sclerosing lesion;
- papillomas.

3. Atypical hyperplasia:
- atypical ductal hyperplasia;
- atypical lobular hyperplasia.
1. NONPROLIFERATIVE BREAST CHANGES (fibrocystic changes) present in 60-80% of women,
in 10% clinically overt, causes 50% of surgical breast procedures. Most frequent between 30
and 50:
FIBROCYSTIC CHANGES, invasive ductal carcinoma of the breast, NST; N85/86

Fibrosis
Cy
sts
al
Norm
s
lobule
LACTATIONAL ADENOMAS; normal-appearing breast tissue with physiologic adenosis and
lactational changes forming palpable masses in pregnant or lactating women.
Probably not true neoplasms.
2. PROLIFERATIVE BREAST DISEASE WITHOUT ATYPIA

- USUAL DUCTAL HYPERPLASIA (UDH, formerly called

epitheliosis); the presence of more than two cell
layers in breast ducts and lobules. An incidental
finding. UDH carries a slightly increased risk (about
1.5–2 fold) for breast cancer.
- PAPILLOMAS; benign epithelial neoplasms composed of multiple branching fibrovascular
cores lined by luminal and myoepithelial cells. Growth occurs within a dilated duct;
central papillomas arise in large ducts (lactiferous sinuses of the nipple, usually solitary),
and peripheral papillomas arise in the TDLU (usually multiple).
Central papillomas produces in more than 80% patients unilateral serous,
sanguineous or serosanguineous nipple discharge. A palpable mass is less frequent.
Galactography!
Central papilloma

Central papilloma
Most small duct papillomas are small palpable masses, or densities or calcifications seen
on mammograms. They may contain a typical or atypical ductal hyperplasia, ductal in situ
carcinoma or even invasive carcinoma (more frequently than central papillomas!).

Peripheral papilloma Peripheral papilloma

3. PROLIFERATIVE BREAST DISEASE WITH ATYPIA; the -
ATYPICAL DUCTAL HYPERPLASIA
- ATYPICAL LOBULAR HYPERPLASIA (ALH) is an incidental finding
Clinical Significance of Benign Epithelial Changes

Both breasts are at increased risk!

Risk reduction can be achieved by bilateral prophylactic mastectomy or treatment with
estrogen antagonists, such as tamoxifen.
More than 80% of women with atypical hyperplasia will NOT develop breast cancer, and
many choose careful clinical and radiologic surveillance over intervention.
PAPUA NEW GUINEA
2

Estimated age-standardised incidence and

mortality rates: women
Risk Factors
Gender; F:M=100:1
Age; a peak incidence at the age of 75–80 years. The average age at diagnosis is 61 for
white women, 56 for Hispanic women, and 46 for African American women (PNG similar).

Early menarche (below the age 11) and late age at menopause.
Age at first live birth; the best age before 20, women over the age of 35 at their first birth
have the risk of nulliparous women. Deliveries before the age of 30 have a protective
effect. Age at first live birth is not a strong risk factor for African American women.
Cumulative breastfeeding exceeding 2 years; the longer women breastfeed, the greater
the reduction in risk.

*It is different in PNG! Cancers are found in younger woman! In the group of 43 patients with histologically confirmed
diagnoses of breast carcinoma (operated in M.H. from 16/07/2015 to 05/01/2017), an average age was 45 years of life,
the youngest patient was 27, and 23/36 (64%) were 45 year-old or younger (the age of 7 patients was unknown).
Risk Factors (cont.)
First-degree relatives with breast cancer (mother, sister, or daughter). About 15% to 20% of
woman with breast cancer have an affected first-degree relative, but do not carry an
identified breast cancer gene mutation. NOTE: the risk is NOT increased if the only
affected relative is a postmenopausal mother with cancer!
A history of prior breast atypical hyperplasia.
Race/ethnicity; non-Hispanic white women have the highest rates of breast cancer. The
incidence of BRCA1 and BRCA2 mutations occur at different frequencies in different ethnic
groups.
Geographic influence; the risk of breast cancer increases in immigrants to the United States
with each generation. Reproductive history (number and timing of pregnancies),
breastfeeding, diet, obesity, physical activity, and environmental factors all probably play a
role.
High breast density; a strong risk factor for developing cancer.
Risk Factors (cont.)
Radiation exposure to the chest (cancer therapy, atomic bomb exposure, or nuclear
accidents); the risk is greatest with exposure at young ages and with high radiation
doses.
Carcinoma of the contralateral breast or endometrium (i.e., an exposure to prolonged
estrogenic stimulation is very likely).
Estrogen exposure; postmenopausal hormone replacement therapy increases the risk of
breast cancer 1.2- to 1.7-fold, and adding progesterone increases the risk further.
Most cancers are ER-positive carcinomas, including invasive lobular carcinomas. Oral
contraceptives have not been shown convincingly to affect breast cancer risk but do
decrease the risk of endometrial and ovarian carcinomas. Reducing endogenous
estrogens by oophorectomy decreases the risk of developing breast cancer by up to
75%. Drugs that block estrogenic effects (e.g., tamoxifen) or block the formation of
estrogen (e.g., aromatase inhibitors) also decrease the risk of ER- positive breast cancer.
Risk Factors (cont.)
Diet; moderate or heavy alcohol consumption increases risk. Higher meat consumption,
particularly red or fried/browned meat is associated with a higher risk. Westernized
diet (high-caloric diet rich in animal fat and proteins) increases the risk. Caffeine
consumption may decrease the risk of breast cancer.
Obesity; decreased risk in obese women younger than 40 years but the risk is increased
for postmenopausal obese women.
Exercise; a probable small protective effect for women who are physically active.
Environmental toxins; definitive associations have yet to be made.
Tobacco smoking; an anti-estrogen and a potential protective factor. But currently, in many
countries more women die from lung cancer than from breast cancer.
Etiology and Pathogenesis
The major risk factors for the development of breast cancer are hormonal and genetic.
Breast carcinomas can therefore be divided into sporadic cases, probably related to
hormonal exposure, and hereditary cases, associated with germline mutations.

Hereditary Breast Cancer (app. 12% of breast cancer); mutations in BRCA1 and BRCA2
(they also increase the risk of developing ovarian carcinoma, esp. BRCA1, additionally
both increase the risk for prostatic and pancreatic carcinomas), Li-Fraumeni syndrome (due
to germline mutations in p53) and Li-Fraumeni variant syndrome (due to germline
mutations in CHEK2), tumor suppressor genes PTEN (Cowden syndrome), LKBI/STK11
(Peutz-Jeghers syndrome), and ATM (ataxia telangiectasia).
Sporadic Breast Cancer; the major risk factors are related to hormone exposure: gender,
age at menarche and menopause, reproductive history, breastfeeding, and exogenous
estrogens. The majority of sporadic cancers occur in postmenopausal women and are ER
positive.
 Precursor not
known –may be Common
lesions progress in PNG?
too quickly to
carcinoma?

Three main pathways of breast cancer development;

The most common pathway (yellow arrow)  ER-positive carcinomas.
A less common pathway (blue arrow)  carcinomas that are negative for ER and HER2.
The third pathway (green arrow)  HER2-positive cancers, which may be ER-positive or ER-negative.
Classification of Breast Carcinoma
Greater than 95% of breast malignancies are adenocarcinomas, which are divided into in
situ carcinomas and invasive (infiltrating) carcinomas.
Carcinoma in situ refers to a neoplastic proliferation that is limited to ducts and lobules by
the basement membrane.
Invasive (infiltrating) carcinoma has penetrated through the basement membrane into
stroma  the cells have the potential to invade into the vasculature and thereby reach
regional lymph nodes and distant sites.
CARCINOMA IN SITU
Ductal Carcinoma in Situ (DCIS; Intraductal Carcinoma); Almost always detected by
mammography
The natural history of DCIS; if untreated, women with small, low-grade DCIS develop
invasive cancer at a rate of about 1% per year.

Morphology; in the past 5

architectural subtypes:
comedocarcinoma, solid,
cribriform, papillary, and
micropapillary. Some cases
of DCIS have a single growth
pattern, but the majority
show a mixture of patterns.
Lobular Carcinoma in Situ (LCIS); 1% to 6% of all carcinomas, always an incidental biopsy
finding.
Women with LCIS develop invasive carcinomas (lobular or ductal type) at a frequency
similar to that of women with untreated DCIS (at about 1% per year). Both breasts are at
increased risk! Treatment choices include bilateral prophylactic mastectomy, tamoxifen, or,
more typically, close clinical follow-up and mammographic screening.
INVASIVE (INFILTRATING) CARCINOMA
In the absence of mammographic screening, invasive carcinoma almost always presents as
a palpable mass. Palpable tumors are associated with axillary lymph node metastases in
over 50% of patients.
Localization; left>right breast (1.07:1.0), 40-50% in the upper outer quadrant, then
central>upper inner>lower outer>lower inner quadrant.
The most common findings in symptomatic women are breast lumps, sometimes painful.
Nipple abnormalities (discharge, retraction, distortion or eczema) are less common and
other forms of presentation are rare.
Breast abnormalities shoud be evaluated by triple assessment including
1. clinical examination,
2. imaging (mammography and ultrasound)
3. tissue sampling by either FNA cytology or needle core biopsy or open
biopsy usually excision biopsy (lumpectomy)
Conditions requiring refferal to a specialist clinic:
Lump; any new discreet mass, a new lump in pre-existing nodularity, assymetrical
nodularity that persists at review after menstruation, abscess on breast inflammation
which does not settle after one course of antibiotics, cyst persistently refilling or recurrent
cyst.
Pain; if associated with a lump, interactable pain that interferes with a patient’s lifestyle or
sleep and which has failed to respond to reassurance, simple measures such as
wearing a well supporting brassiere and common drugs, unilateral persistent pain in
postmenopusal women.
Nipple discharge; all women more than 50, women less than 50 with bilateral discharge
sufficient to stain clothes, bloodstained discharge, persistent single duct discharge.
Nipple retraction, distortion, eczema.
Change in breast contour.
Family history of breast cancer.
In older women undergoing mammography, invasive
carcinomas most commonly present as a radiodense
mass. Mammographically detected cancers are, on
average, half the size of palpable cancers (the average
size of an invasive carcinoma detected by palpation is
2.4 cm, by mammography - 1.1 cm).
Fine Needle Aspiration (FNA)
Larger carcinomas may be fixed to the chest wall or cause dimpling of the skin. When the
tumor involves the central portion of the breast, retraction of the nipple may develop.
Lymphatics may become so involved as to block the local area of skin drainage and cause
lymphedema and thickening of the skin. In such cases, tethering of the skin to the breast by
Cooper ligaments mimics the appearance of an orange peel, an appearance referred to as
peau d’orange.
Special clinical forms;
- inflammatory carcinoma (tumors that
present with a swollen, erythematous
breast, increased density (hard)). This
gross appearance is caused by extensive
invasion and obstruction of dermal
lymphatics by tumor cells.
- Paget disease of the nipple is a rare manifestation of breast cancer (1% to 4% of cases)
and presents as a unilateral erythematous eruption with a scale crust. Pruritus is common,
and the lesion may be mistaken for eczema. Malignant cells (Paget cells) extend from DCIS
within the ductal system, via the lactiferous sinuses, into nipple skin without crossing
the basement membrane. The Paget cells are readily detected by nipple biopsy or
cytologic preparations of the exudate.
A palpable mass is present in 50% to 60% of women with Paget disease, and almost all
of these women have an underlying invasive carcinoma.
- carcinoma eu cuirasse; chronic skin edema and
fibrosis  skin ulceration and satellite nodules.
Most commonly associated with breast
carcinoma with local recurrence after
mastectomy
Distant spread;
- via lymphatics; axillary
lymph nodes, supraclavicular
l.n., along the internal
mammary arteries.
- hematogenous; lungs, bones
(osteoblastic and
osteolytic mm.), liver,
adrenals, brain and others.

Rarely, breast cancer presents

as an axillary nodal metastasis
or distant metastasis before
cancer is detected in the
breast.
There is a wide range of histologic appearances.
Well-differentiated carcinomas (G1) show prominent tubule formation, small round
nuclei, and rare mitotic figures.
Moderately differentiated carcinomas (G2) may have tubules, but solid clusters or single
infiltrating cells are also present. These tumors have a greater degree of nuclear
pleomorphism and contain mitotic figures.
Poorly differentiated carcinomas (G3) often invade as ragged nests or solid sheets of cells
with enlarged irregular nuclei. A high proliferation rate and areas of tumor necrosis
are common.
INVASIVE LOBULAR CARCINOMA
Usually presents as a palpable mass or a mammographic density with irregular borders.
However, in about 1/4 of cases the tumor infiltrates the tissue diffusely and causes little
desmoplasia. They are difficult to detect by palpation and may cause only very subtle
mammographic changes. Metastases can also be difficult to detect clinically and
radiologically because of this type of invasion.
Morphology; dyscohesive infiltrating tumor cells, often
arranged in single file (Indian file pattern), targetoid
pattern around ducts, or in loose clusters or sheets. Tubule
formation is absent. The cytologic appearance is identical to
the cells of ALH and LCIS. Signet-ring cells containing an
intracytoplasmic mucin droplet are common. Desmoplasia
may be minimal or absent.
MEDULLARY CARCINOMA
A well circumscribed carcinoma composed of poorly diferentiated cels arranged in large
sheets with no glands, scant stroma and a prominent lymphoplasmacytic infiltrate.
Morphology; the tumor is soft, fleshy (medulla oblongata-like).Histologically, the carcinoma
is characterized by (1) solid, syncytium-like sheets of large cells with vesicular, pleomorphic
nuclei, and prominent nucleoli, which compose more than 75% of the tumor mass; (2)
frequent mitotic figures; (3) a moderate to marked lymphoplasmacytic infiltrate surrounding
and within the tumor; and (4) a pushing (noninfiltrative) border. All medullary carcinomas
are poorly differentiated.
Medullary carcinomas have a slightly better prognosis than do NST carcinomas.
PROGNOSTIC AND PREDICTIVE FACTORS
TNM staging system (American Joint Committee on Cancer, AJCC) is correlated with
survival.
The major prognostic factors are as follows:
1. Invasive carcinoma versus in situ disease.
2. Distant metastases (M); in M1 patients cure is unlikely.
3. Lymph node metastases (N); the most important prognostic factor for invasive
carcinoma in the absence of distant metastases.
4. Histological characteritics
The clinical assessment of lymph node status is unreliable due to both false positives
(e.g., palpable reactive nodes) and false negatives (e.g., lymph nodes with small
metastatic deposits).
The 10-year disease-free survival rate for pN0 patients - 70% to 80%; pN1 - 35% to 40%
(one to three positive nodes), pN3 - 10% to 15% (more than 10 nodes are positive).
Lymphatic vessels in most
breast carcinomas drain first
to one or two sentinel nodes,
which can be identified with
radiotracer or colored dyes.
When (-), the patient can be
spared the morbidity of a
complete axillary dissection.
In some tumors of the medial
breast, the sentinel node is an
intrathoracic internal
mammary node. These nodes
are generally not biopsied
owing to the morbidity
associated with the procedure.
4. Tumor size; the second most important prognostic factor. The risk of axillary lymph
node metastases increases with the size of the primary tumor, but both are
independent prognostic factors. Women with pN0 carcinomas <1 cm in size have a 10-
year survival rate of over 90%, whereas survival drops to 77% for cancers >2 cm.
5. Locally advanced disease now are rare at initial presentation.

6. Inflammatory carcinoma (with breast swelling and skin thickening due to dermal
lymphatic involvement) have a particularly poor prognosis. The 3-year survival rate is
only 3% to 10%. Less than 3% of cancers are in this group, but the incidence is higher
in African American women and younger women.
TNM Clinical Classification

T – Primary Tumour
TX Primary tumour cannot be assessed

T0 No evidence of primary tumour

Tis Carcinoma in situ
Tis (DCIS) Ductal carcinoma in situ
Tis (LCIS) Lobular carcinoma in situ
Tis (Paget) Paget disease of the nipple with no tumour

Note: Paget disease associated with a tumour is classified according to

the size of the tumour
T1 Tumour 2 cm or less in greatest dimension
T1mi Microinvasion 0.1 cm or less in greatest dimensiona
T1a More than 0.1 cm but not more than 0.5 cm in greatest
dimension
T1b More than 0.5 cm but not more than 1 cm in greatest
dimension
T1c More than 1 cm but not more than 2 cm in greatest
dimension
T2 Tumour more than 2 cm but not more than 5 cm in greatest
dimension
T3 Tumour more than 5 cm in greatest dimension
T4 Tumour of any size with direct extension to chest wall or skin
only as described in T4a to T4d
Note: Chest wall includes ribs, intercostal muscles, and serratus anterior
muscle but not pectoral muscle.
T4a Extension to chest wall
T4b Oedema (including peau d’orange), or ulceration of the skin of the
breast, or satellite skin nodules confined to the same breast
T4c Both 4a and 4b, above
T4d Inflammatory carcinoma
N – Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed (e.g. previously

removed)

N0 No regional lymph node metastasis

N1 Metastasis in movable ipsilateral axillary lymph node(s)
N2 Metastasis in fixed ipsilateral axillary lymph node(s) or in
clinically apparent* ipsilateral internal mammary lymph node(s) in
the absence of clinically evident axillary lymph node metastasis

N2a Metastasis in axillary lymph node(s) fixed to one another or

to other structures
N 2b Metastasis only in clinically apparent* internal mammary
lymph node(s) and in the absence of clinically evident axillary
lymph node metastasis
N3 Metastasis in ipsilateral infraclavicular lymph node(s) with or
without axillary lymph node involvement; or in clinically
apparent* ipsilateral internal mammary lymph node(s) in the
presence of clinically evident axillary lymph node metastasis;
or metastasis in ipsilateral supraclavicular lymph node(s) with or
without axillary or internal mammary lymph node involvement

N3a Metastasis in infraclavicular lymph node(s)

N3b Metastasis in internal mammary and axillary lymph nodes
N3c Metastasis in supraclavicular lymph node(s)
Note: * clinically apparent = detected by clinical examination or by imaging studies (excluding
lymphoscintigraphy)
M – Distant Metastasis

MX Distant metastasis cannot be assessed

M0 No clinical or radiographic evidence of distant metastasis
cM0(i+) No clinical or radiographic evidence of distant metastases, but
deposits of molecularly or microscopically detected tumor cells in
circulating blood, bone marrow, or other nonregional nodal tissue that
are no larger than 0.2 mm in a patient without symptoms or signs of
metastases
M1 Distant detectable metastases as determined by classic clinical and
radiographic means and/or histologically proven > 0.2 mm
pTNM Pathological Classification
pT – Primary Tumour
The pathological classification requires the examination of the primary
carcinoma with no gross tumour at the margins of resection. A case can
be classified pT if there is only microscopic tumour in a margin.
pT categories = T categories.
Note: When classifying pT the tumour size is a measurement of the invasive component.
If there is a large in situ component (e.g. 4 cm) and a small invasive component
(e.g. 0.5 cm), the tumour is coded pT1a.
pN – Regional Lymph Nodes
pNX Regional lymph nodes cannot be assessed (not removed for study or
previously removed)
pN0 No regional lymph node metastasis [cases with only isolated tumour cells (ITC) in regional
lymph nodes are classified as pN0. ITC are single tumour cells or small clusters of cells, not more than
0.2mm in greatest dimension, that are usually detected by immunohistochemistry or molecular methods but
which may be verified on H&E stains. ITCs do not typically show evidence of metastatic activity (e.g.,
proliferation or stromal reaction)].
pN1mi Micrometastasis (larger than 0.2 mm, but none larger than 2 mm in greatest
dimension)
pN1 Metastasis in 1 - 3 ipsilateral axillary lymph node(s), and/or in internal
mammary nodes with microscopic metastasis detected by sentinel lymph node
dissection but not clinically apparent [not detected by clinical examination or by imaging studies
(excluding lymphoscintigraphy)].
pN1a Metastasis in 1-3 axillary lymph node(s), including at least one larger than
2 mm in greatest dimension
pN1b Internal mammary lymph nodes with microscopic metastasis detected by
sentinel lymph node dissection but not clinically apparent
pN1c Metastasis in 1 - 3 axillary lymph nodes and internal mammary lymph nodes
with microscopic metastasis detected by sentinel lymph node dissection but
not clinically apparent
pN2 Metastasis in 4 - 9 ipsilateral axillary lymph nodes, or in
clinically apparent [clinically apparent = detected by clinical examination or by
imaging studies (excluding lymphoscintigraphy) or grossly visible pathologically]
ipsilateral internal mammary lymph node(s) in the absence of
axillary lymph node metastasis
pN2a Metastasis in 4-9 axillary lymph nodes, including at least one
that is larger than 2 mm
pN2b Metastasis in clinically apparent internal mammary lymph
node(s), in the absence of axillary lymph node metastasis.
pN3 Metastasis in 10 or more ipsilateral axillary lymph nodes; or in infraclavicular
lymph nodes; or in clinically apparent ipsilateral internal mammary lymph nodes
in the presence of one or more positive axillary lymph nodes; or in more than 3
axillary lymph nodes with clinically negative, microscopic metastasis in internal
mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes
pN3a Metastasis in 10 or more axillary lymph nodes (at least one larger than 2 mm)
or metastasis in infraclavicular lymph nodes
pN3b Metastasis in clinically apparent internal mammary lymph node(s) in the
presence of one or more positive axillary lymph node(s); or metastasis in more than
3 axillary lymph nodes and in internal mammary lymph nodes with microscopic
metastasis detected by sentinel lymph node dissection but not clinically apparent
pN3c Metastasis in supraclavicular lymph node(s).

pM – Distant Metastases
pM categories = M categories
Stage T: Primary Cancer Lymph Nodes (LNs) M: Distant Metastasis 5-Year Survival (%)
0 DCIS or LCIS (Tis) No metastases (N0) Absent (M0) 92
I Invasive carcinoma ≤2 cm (T0, T1) No metastases (N0) Absent (M0) 87
II Invasive carcinoma No metastases (N0) Absent (M0) 75
>2 cm (T2)
Invasive carcinoma 1 to 3 positive LNs (N1) Absent (M0)
<5 cm (T1, T2)
III Invasive carcinoma 1 to 3 positive LNs (N1) Absent (M0) 46
>5 cm (T3)
Any size invasive carcinoma ≥4 positive LNs Absent (M0)
(T0, T1, T2, T3) (N2, N3)
Invasive carcinoma with skin or 0 to >10 positive LNs Absent (M0)
chest wall involvement or (N0, N1, N2, N3)
inflammatory carcinoma (T4)
IV Any size invasive carcinoma Negative or positive Present (M1) 13
(T0, T1, T2, T3, T4) lymph nodes
(N0, N1, N2, N3)
9. Estrogen and progesterone receptors (ER & PR);
their presence is correlated with a better
outcome and is an important predictor of
response to hormonal therapy. Eighty percent of
carcinomas that are ER and PR positive respond
to hormonal manipulation, whereas only about 40%
of those with either ER or PR alone respond. ER-
positive cancers are less likely to respond to
chemotherapy. Conversely, cancers that fail to
express either ER or PR have a less than 10%
likelihood of responding to hormonal therapy but
are more likely to respond to chemotherapy.
10. HER2/neu; HER2/neu overexpression is associated with poorer survival, but its main
importance is as a predictor of response to agents that target this transmembrane
protein (e.g., trastuzumab or lapatinib).

11. Lymphovascular invasion; a poor prognostic factor for overall survival in women
without lymph node metastases and a risk factor for local recurrence.
12. Proliferative rate.
13. DNA content.
14. Response to adjuvant therapy.
15. Gene expression profiling; it has been shown to predict survival and recurrence-free
interval, and also identifies patients who are most likely to benefit from particular types
of chemotherapy.
Current therapeutic approaches
directed at local and regional
control consist of combinations of
surgery (mastectomy or breast
conservation) and postoperative
radiation, whereas attempts at
systemic control rely on hormonal
treatment, chemotherapy, or both.
Axillary node dissection or sentinel
node sampling is performed for
prognostic purposes, but the axilla
can also be treated with radiation
alone. Newer therapeutic
strategies include inhibitors of
membrane-bound growth factor
receptors (e.g., HER2/neu), stromal
proteases, and angiogenesis.
FIBROADENOMA (FA)
The most common benign tumor of the female breast. Most occur in women in their 20s
and 30s, and they are frequently multiple and bilateral.
Morphology; spherical nodules that are usually sharply circumscribed and freely movable.
The tumors are well-circumscribed, rubbery, grayish white nodules that bulge above the
surrounding tissue and often contain slitlike spaces.
They vary in size from less than 1 cm to large tumors that can replace most of the breast.
In FNA - moose antlers-like appearance.
PHYLLODES TUMOR (PT, cystosarcoma phyllodes)
A group of circumscribed biphasic tumors, basically analogous to FAs, characterized by a
double layered epithelial component arranged in clefts surrounded by an overgrowing
hypercellular mesenchymal component, typically organized in leaf-like structures.
They can occur at any age, most present in the sixth decade (10 to 20 years later than the
peak age for fibroadenomas). The majority are detected as palpable masses, but a few are
found by mammography. The majority of these tumors behave in a relatively benign
fashion, and most are not cystic. They may develop de novo or from FAs.
Morphology; PTs tend to grow quickly, within a period of weeks or months, to a size of 2-3
cm or sometimes larger. This rapid growth does not automatically mean the phyllodes tumor
is malignant; benign tumors can grow quickly, too. The tumors vary in size from a few
centimeters to massive lesions involving the entire breast. The larger lesions often have
bulbous protrusions due to the presence of nodules of proliferating stroma covered by
epithelium (sometimes protruding into a cystic space).
 INFLAMMATORY DISORDERS
Less than 1% of women with breast symptoms. Women usually present with an
erythematous swollen painful breast.
“Inflammatory breast cancer” mimics inflammation by obstructing dermal vasculature
with tumor emboli, resulting in an enlarged erythematous breast, and should always be
suspected in a nonlactating woman with the clinical appearance of mastitis.

Inflammatory breast cancer

ACUTE MASTITIS
The first month of breastfeeding (the development of cracks and fissures in the
nipples!).
Causes: Staphylococcus aureus, less commonly, streptococci.
The breast is erythematous and painful, fever is often present.
Morphology; staphylococcal infections: usually produce a localized area of acute
inflammation  the formation of single or multiple abscesses. Streptococcal
infections: tend to cause (as elsewhere) a diffuse spreading infection.
Most cases of lactational mastitis are usually easily treated with appropriate
antibiotics.
Scarring  cancer-like.
FAT NECROSIS (traumatic, not enzymatic)
A painless palpable mass, skin thickening or retraction, a mammographic density, or mammographic calcifications. The majority of affected women have a history of breast trauma or prior surgery.
Morphology:

As with other inflammatory breast disorders, the major clinical significance of the condition is its possible confusion with breast cancer.
GRANULOMATOUS MASTITIS
Rare - in less than 1% of all breast biopsy specimens: in
systemic granulomatous diseases (e.g., Wegener
granulomatosis or sarcoidosis), granulomatous infections
caused by mycobacteria or fungi. Infections of this type
are most common in immunocompromised patients or
adjacent to foreign objects such as breast prostheses or
nipple piercings.
Granulomatous lobular mastitis - an uncommon breast-
limited disease that only occurs in parous women. The
granulomatous inflammation is confined to the lobules,
suggesting that it is caused by a hypersensitivity reaction
to antigens expressed by lobular epithelium during
lactation.
1. AMASTIA
2. MILKLINE REMNANTS
Accessory axillary breast tissue
Verhoeven P: Total recall. 1990
4. CONGENITAL NIPPLE INVERSION
IMPORTANT SYMPTOMS

Breast pain (mastalgia)

As for pain at any other site, you should establish the site, radiation, character, duration, severity, exacerbating factors,
relieving factors, and associated symptoms.
The most common cause of mastalgia in premenopausal women is
hormone-dependent change. Other benign causes include mastitis and
abscesses. One in 100 breast cancers presents with mastalgia as
the sole symptom.
Nipple discharge
Important causes of nipple discharge include ductal pathology, such as ductal ectasia, papilloma, and carcinoma.
Ask about the following:
• Is the discharge true milk or some other substance?
• What color is the discharge (e.g., clear, white, yellow, blood-stained)?
• Is it spontaneous or nonspontaneous?
• Is the discharge unilateral or bilateral?
• Are there any changes in the appearance of the nipple or areola?
• Mastalgia?
• Are there any breast lumps?
• Periareolar abscesses or fistulae indicating periductal mastitis? This is
closely linked to smoking in young women. Periductal mastitis
is also associated with hidradenitis suppuritiva. Ask about
abscess elsewhere, e.g., axilla and groin. The symptoms are
often recurrent.

Remember that after childbearing, some women continue to discharge a small

secretion of milk (galactorrhea). However, in rare instances this can be the first
presenting symptom of a prolactin-secreting pituitary adenoma. In the case of true bilateral galactorrhea, you should also
ask about
• Headaches
• Visual disturbances, especially visual field deficits
Breast palpable discrete mass
These are a very important presenting complaint with a number of causes, the most important one being cancer. Establish
the following:
• When the lump was first noticed
• Whether the lump has remained the same size or enlarged
• Whether the size of the lump changes according to menstrual cycle
• Is there any pain?
• Are there any local skin changes?
• Is there a history of breast lumps (ask about previous biopsies, diagnoses, and operations)?
• A full systems inquiry should include any other symptoms that might suggest a neoplastic disease (weight loss,
loss of appetite, fatigue, etc.) and metastatic spread to other organ systems (shortness of breath, bony pain, etc.).

„Lumpiness” (without a discrete mass) = the normal nodularity!

Lymph nodes
Lymphatic drainage from the medial
portion of the breast is to the internal
mammary nodes. The central and
lateral portions drain to the axillary
lymph nodes, which are arranged into
six groups: lateral, pectoral (anterior),
central, subcapsular (posterior),
infraclavicular (deltopectoral), apical.
Support the patient’s arm. For example, when examining the right axilla,
abduct the patient’s right arm gently and support it at the wrist with your
right hand while examining the axilla with your left hand.
If you feel any lymph nodes, consider site, size, number, consistency,
tenderness, fixation, and overlying skin changes.
Remember to also palpate for lymph nodes in the lower deep cervical
lymph chain at the same time as the supraclavicular nodes.
!!!!!!!!!!!!!!!!!!!!
Breast cancer - presenting symptoms
The presenting symptoms may be related to the primary lesion. For example:
• Palpable mass
• Pain (1/100 cancers present with mastalgia only)
• Nipple discharge, retraction, or rash
• Dimpling of the breast tissue
• Local edema
The presenting symptom may be related to the effects of secondary spread. For example:
• Arm swelling (lymphatic or venous obstruction)
• Backache (skeletal infiltration)
• Malaise
• Loss of weight
• Dyspnea
• Cough
• Nodules in skin
• Jaundice
• Mental changes
• Seizures
• Symptoms of hypercalcemia (e.g., thirst)
MALE BREAST
CARCINOMA
The overall incidence in men is only 1% of that in women (a lifetime risk of 0.11%).
Risk factors are similar to those in women and include first-degree relatives with breast
cancer, decreased testicular function (e.g., Klinefelter syndrome), exposure to exogenous
estrogens, increasing age, infertility, obesity, prior benign breast disease, exposure to
ionizing radiation, and residency in Western countries. Germline BRCA2(!) and BRCA1
mutations. From 3% to 8% of cases are associated with Klinefelter syndrome.
Nipple discharge is a common symptom. The carcinoma is situated close to the overlying
skin and underlying thoracic wall, and even small carcinomas can invade these structures
and ulcerate through the skin.