Cáncer de Mama:

Principios Básicos

Dr. Byron Sánchez Romero

Medicenter-Guatemala
No todo es cáncer…….

12/08/21
 Warning Signs
Warning signs and symptoms:
• Painless lump or thickening
• Thickening or swelling that persist
• Nipple pain or retraction
• Breast skin irritation or dimpling
• Spontaneous discharge

Early breast cancer

may not have symptoms.
 Global Differences in Breast Cancer
Diagnosis and Outcomes: Survival
► Estimated mortality-to-incidence ratios are
generally lower in developed regions1
USA (83–88%)2*

ASR 5-year survival

Europe (60–83%)2*

Developing countries
(45–72%)3**

Women diagnosed: *1990–1994; 1982–1992

**

1
Shibuya, et al. BMC Cancer 2002;2:37; 2Coleman, et al. Ann Oncol 2003;14
(Suppl 5):V128–V149; 3Sankaranarayanan, et al. IARC Sci Publ 1998;145:135–73
 GLOBAL STATISTICS:
Mortality vs. Degree of economic
development

More developed countries Less developed countries

0.33 (189 deaths / 579 cases ) 0.39 (184 deaths / 471 cases)

SLIDE CREDIT:Gilberto
Schwartsmann
 2009 Estimated US Cancer Cases*
Men Women
766,130 713,220
Prostate 25% 27% Breast
Lung & bronchus 15% 14% Lung & bronchus
Colon & rectum 10% 10% Colon & rectum
Urinary bladder 7% 6% Uterine corpus
Melanoma of skin 5% 4% Non-Hodgkin
lymphoma
Non-Hodgkin5%
lymphoma 4% Melanoma of skin
Kidney & renal pelvis 5% 4% Thyroid
Leukemia 3% 3% Kidney & renal pelvis
Oral cavity 3% 3% Ovary
Pancreas 3% 3% Pancreas
All Other Sites 19% 22% All Other Sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2009.
 Cancer Incidence Rates* Among Men, US, 1975-2005

Rate Per 100,000

250

Prostate
200

150

Lung & bronchus

100

Colon and rectum

50 Urinary bladder

Non-Hodgkin lymphoma
Melanoma of the skin
0
1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005

*Age-adjusted to the 2000 US standard population and adjusted for delays in reporting.
Source: Surveillance, Epidemiology, and End Results Program, Delay-adjusted Incidence database:
SEER Incidence Delay-adjusted Rates, 9 Registries, 1975-2005, National Cancer Institute, 2008.
 Cancer Incidence Rates* Among Women, US, 1975-2005

Rate Per 100,000

250

200

150 Breast

100

Colon and rectum Lung & bronchus

50
Uterine Corpus
Ovary
Non-Hodgkin lymphoma
0
1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005

*Age-adjusted to the 2000 US standard population and adjusted for delays in reporting.
Source: Surveillance, Epidemiology, and End Results Program, Delay-adjusted Incidence database:
SEER Incidence Delay-adjusted Rates, 9 Registries, 1975-2005, National Cancer Institute, 2008.
 2009 Estimated US Cancer Deaths*

Lung & bronchus 30% Men Women 26% Lung & bronchus
292,540 269,800
Prostate 9% 15% Breast
Colon & rectum 9% 9% Colon & rectum
Pancreas 6% 6% Pancreas
Leukemia 4% 5% Ovary
Liver & intrahepatic 4% 4% Non-Hodgkin
bile duct lymphoma
Esophagus 4% 3% Leukemia
Urinary bladder 3% 3% Uterine corpus
Non-Hodgkin 3% 2% Liver & intrahepatic
lymphoma bile duct
Kidney & renal pelvis 3% 2% Brain/ONS
All other sites 25% 25% All other sites

ONS=Other nervous system.

Source: American Cancer Society, 2009.
Breast Cancer Facts
 2nd leading cause of death
 2nd most common cancer
Incidence increases with
age
 All women are at risk
Breast Cancer in USA

One out of eight American

women will be diagnosed
with breast cancer
 Breast Cancer Risk Factors
that cannot be changed
Age
GENDER - All Reproductive
women are History
Family/Personal
at risk
History

Menstrual
Race History
Radiation
Treatment with Genetic
DES Factors
Breast Cancer Risk Factors
that can be controlled
Obesity
All Not having
Exercise women are children
at risk

Breastfeeding
Birth Control
Hormone Pills
Alcohol Replacement
Therapy
 Hereditary Breast Cancer
About 15% of breast cancers are inherited
Approximately 80% of hereditary breast cancer is caused by
mutations in the BRCA1 or BRCA2 genes
Women who inherit a BRCA mutation have a 50% to 85%
chance of developing breast cancer in their lifetime
Women with especially strong family history may consider
preventive surgery to remove breast tissue and/or
chemoprevention
Several other genetic syndromes can increase breast cancer
risk
Genetic counseling and testing is available for most
syndromes
What is the Structure of the Breast?
The breast is composed mainly of fatty
tissue, which contains a network of
lobes made up of tiny, tube-like
structures called lobules that contain
milk glands

Tiny ducts connect the glands, lobules,

and lobes, and carry the milk from the
lobes to the nipple

Blood and lymph vessels run

throughout the breast

About 90% of all breast cancers

originate in the ducts or lobes of the
breast
Mammary gland
development
Breast Anatomy

Breast profile:
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major muscle
G chest wall/rib cage

Enlargement:
A normal duct cells
B basement membrane
C lumen (center of duct)

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Triple Assessment

– Clinical Evaluation – Lump and regional

nodes
– Imaging (ultrasound <35 years old or
mammography >35 years old)
– Cytology or Histology

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A Good Breast Health
Plan
1. Mammograms
2. Clinical Breast
Examination
(CBE)
3. Self Awareness
(Monthly Self
Exams) (BSE)
 American Cancer Society
Screening Recommendations
 Annual mammograms,

 starting at age 40
 Panel Puts Off Mammography until
Age 50
 Clinical breast exams
– every year starting at age 40
– every 3 years for women age
20-39
 Self-breast exams monthly, starting at
age 20
Mammography

Average-size lump found by woman

practicing occasional breast self-exam
(BSE)

Average-size lump found by woman

practicing regular breast self-exam
(BSE)

Average-size lump found by first

mammogram

Average-size lump found by getting

regular mammograms
Mitos…….
STANDARDIZED BREAST
EXAMINATION

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Malignant masses

 Hard
 Painless: Malignant masses are painful in only 10-
15% of patients.
 Irregular
 Skin dimpling
 Nipple retraction
 Bloody or watery discharge
 Possibly fixed to the skin or chest wall

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 Inflammatory

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Breast imaging

 The breast can be imaged

with mammography,
ultrasound or MRI
 Mammography is the most
sensitive of breast imaging
modalities
 Sensitivity is reduced in young
women due to the presence
of increased glandular tissue
 For symptomatic patients,
imaging always be performed
as part of triple assessment

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 Breast ultrasound
 Ultrasound is useful in the
assessment of breast
lumps
 Complements
mammography and is able
to differentiate solid and
cystic lesions
 Also able to guide fine
needle aspiration and core
biopsies
 Can be used to assess
tumour size and response
to therapy
 In the diagnosis of
malignancy it has a
sensitivity and specificity
of 75% and 97%
respectively
 Cysts and solid lesions
have typical appearances
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 CBC count with differential and
platelet count
 Chemistry and renal function studies
 Liver function tests
 Calcium and phosphorus evaluations

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 Chest radiograph
 CT scan of the brain, chest, abdomen, and
pelvis: Obtain CT scans if the patient has
neurologic symptoms, abnormal chest
radiograph results, supraclavicular
lymphadenopathy and hepatosplenomegaly,
or abnormal liver function test results.
 Skeletal radiograph: Use this for
symptomatic areas only.
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Immunohistochemistry in Breast Cancer
Diagnosis & Prognosis

ER-positive Tumor HER-2-Overexpressing

Tumor
 Breast Cancer Up Until Now:
Testing for 1 or 2 Specific Molecules

Estrogen Receptor: 75% of HER-2: 20-25% of breast

breast cancers are ER+ cancers are HER-2+
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Breast Cancer and the Bone
Microenvironment
• The skeleton is the initial
site of recurrence in 35-
40% of breast cancer
patients

• Incidence of bone
metastases in advanced
breast cancer is 65-75%
Breast Cancer and Bisphosphonates
(Inhibitors of Bone Breakdown)

Growth factors

osteoblasts,
macrophages

breast cancer osteoclasts

cells Growth factors
 Bisphosphonates in Treating
Bone Metastases
• Several bisphosphonates approved
throughout the world for treatment of
reducing in skeletal-related
complications or symptoms in patients
with bone metastases
– clodronate (Bonefos): oral
– pamidronate (Aredia): IV - US
– zoledronic acid (Zometa): IV - US
– Ibandronate (Bondronat): IV, oral
Zoledronic Acid vs. Placebo in Stage IV
Breast Cancer with Bone Metastases
Kohno N et al, J Clin Oncol 23, 2005
49.6
38.9
40
35 29.8
30
Patients, %

25 25.4
17.7
20
15 8.8 11.5
8.8
10 3.5
2.6
5
0
All SREs Radiation to Fractures Spinal cord HCM
bone compression
Zoledronic acid 4 mg (n = 114) Placebo (n=113)

Events at 12 Months
Zoledronic Acid (Zometa) vs. Placebo in
Stage IV Breast Cancer
Pain Scores (Brief Pain Inventory)
Kohno N et al, J Clin Oncol 23, 2005
TNM system

Based on anatomical extent of spread

-T refers to the extent of primary tumor

-N refers to the extent of nodal metastases

-M refers to the presence or absence of distant metastases

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 TX – Primary tumour cannot be assessed
T0 – No evidence of primary tumour
Tis – Carcinoma in situ: intraductal
carcinoma or lobular carcinoma in situ, or
Paget’s disease of the nipple with no
tumour*
T1 – Tumour 2 cm in greatest dimension
T1a 0.5 cm in greatest dimension
T1b >0.5 cm to 1 cm in greatest dimension
T1c >1cm to 2cm in greatest dimension
T2 – Tumour >2 cm and 5 cm in greatest
dimension
T3 – Tumour >5 cm in greatest dimension
T4 – Tumour of any size with direct
extension to chest wall or skin
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 T4a and T4b above
T4d Inflammatory carcinoma
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*
 N Categories
NX – Regional lymph nodes cannot be
assessed
N0 – No regional lymph nodes
metastasis
N1 – Metastasis to movable ipsilateral
axillary lymph node(s)
N2 – Metastasis to ipsilateral axillary
lymph node/s fixed to one another or to
other structures
N3 – Metastasis to ipsilateral internal
mammary lymph node(s)
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 Pathologic Classification (pN)*

pNX – Regional lymph nodes cannot be

assessed (e.g. previously removed, or not
removed for pathologic study)
pNO – No regional lymph node metastasis
pN1 – Metastasis to moveable ipsilateral
axillary lymph node(s)
pN2 – Metastasis to ipsilateral axillary lymph
nodes that are fixed to one
another or to other structures
pN3 – Metastasis to ipsilateral internal
mammary lymph node(s)

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 M Categories
MX – Presence of
distant metastasis
cannot be assessed
M0 – No distant
metastasis
M1 – Distant
metastasis
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 Stage 0 Breast Cancer
Known as “cancer in situ,” meaning the cancer has not
spread past the ducts or lobules of the breast (the natural
boundaries)

Also called noninvasive cancer

Ductal carcinoma in situ (DCIS) is the most common in

situ breast cancer
Stage I Breast Cancer

The tumor is small (2

cms) and has not spread
to the lymph nodes
Stage IIa Breast Cancer
Stage IIa breast cancer
describes a smaller tumor
that has spread to the
axillary lymph nodes
(lymph nodes under the
arm), or a medium-sized
tumor that has not spread
to the axillary lymph nodes
Stage IIa may also describe
cancer in the axillary lymph
nodes with no evidence of a
tumor in the breast
Stage IIb Breast Cancer

Stage IIb breast cancer

describes a medium-sized (2
a 5 cms) tumor that has
spread to the axillary lymph
nodes
Stage IIb may also describe a
larger tumor that has not
spread to the axillary lymph
nodes
Stage IIIa Breast Cancer

Stage IIIa breast cancer

describes any size (>
5mcs) tumor that has
spread to the lymph
nodes
Stage IIIb Breast Cancer

Stage IIIb breast cancer

has spread to the chest
wall, or caused swelling or
ulceration of the breast, or
is diagnosed as
inflammatory breast
cancer
Stage IIIc Breast Cancer

Stage IIIc breast cancer

has spread to distant
lymph nodes but has
not spread to distant
parts of the body
 Stage IV Breast Cancer
Stage IV breast cancer can be any size and has
spread to distant sites in the body, usually the
bones, lungs or liver, or chest wall
Breast Cancer Treatments
• Surgery
• Chemotheraphy
• Radiation Therapy
• Hormone Theraphy
• Immunotherapy
 Treatment

Local-Regional Systemic

Surgery +/- Radiation Hormonal Chemoteraphy

for ER+
Tipos de Terapia:

Neoadyuvante

Adyuvante

Paliativa
Consideraciones
importantes:
 Pre-Post menopáusica
 Estatus hormonal y HER2
 Enfermedad temprana
 Enfermedad avanzada o metastásica

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Surgery:
 Woman with
lumpectomy

A Tumor (dark
area)
B Tissue removed
at lumpectomy
(light pink)

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 Biopsy: Margins of Resection

 Negative and positive "margins" or

"margins of resection" (the
distance between the tumor and
the edge of the tissue).
 A cancer cells
 B normal tissue
 C ink marking the edge

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Simple Mastectomy

Woman with total (simple) mastectomy.

A pink highlighted area indicates tissue
removed at mastectomy
B axillary lymph nodes: levels I
C axillary lymph nodes: levels II
D axillary lymph nodes: levels III

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Radical Mastectomy

 Woman with radical

mastectomy.
 A pink highlighted area
indicates tissue removed at
mastectomy
 B axillary lymph nodes: levels
I
 C axillary lymph nodes: levels
II
 D axillary lymph nodes: levels
III
 E supraclavicular lymph nodes
 F internal mammary lymph
nodes

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Modified Radical
Mastectomy
 Woman with modified
radical mastectomy.
 A pink highlighted area
indicates tissue removed at
mastectomy
 B axillary lymph nodes:
levels I
 C axillary lymph nodes:
levels II
 D axillary lymph nodes:
levels III

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 Blue Dye
 A blue dye in lumpectomy
site
 B axillary lymph nodes: levels
I
 C axillary lymph nodes: levels
II
 D axillary lymph nodes: levels

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REQUISITO:

Poseer Receptores
de Estrógeno
POSITIVOS !!!

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 Drugs Targeting Estrogen and It’s Receptor
in Breast Cancer
Aromatase SERMS (tamoxifen,
inhibitors, ovarian raloxifene), SERDS
suppression (fulvstrant)

Cell
Growth
Estrogen Estrogen
and
Receptor
Division
 Aromatase Inhibitors
Adrenal Hormones

Cortisol Androstenedione Aldosterone

Estrone Testosterone

Aromatase inhibitors Estradiol Anastrozole (Arimidex)

block post-menopausal Letrozole (Femara)
estrogen production Exemestane (Aromasin)
Indicaciones:

 POSTMENOPÁUSICAS

 Enfermedad Temprana
 Neoadyuvancia (no FDA)

 Adyuvancia

 Adyuvancia Extendida

 Enfermedad metastásica
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Drogas orales
disponibles:
 TAMOXIFENO

 LETROZOLE

 ANASTRAZOLE

 EXEMESTANE

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 Desarrollo Femara:

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Pico de recurrencias post
cirugía:

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Met´s a distancia
disminuyen la sobrevida:

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 TAMOXIFEN 5 ys

LETROZOLE 5 ys
BIG 1-98
n=8028 TAMOXIFEN 2 ys LETROZOLE 3 ys

LETROZOLE 2 ys TAMOXIFEN 3 ys

TAMOXIFEN 5 ys
IES
n=4740 TAMOXIFEN 2-3 ys EXEMESTANE 2-3 ys

ABCSG8/ TAMOXIFEN 5 ys
ARNO95
n=3901+1059 TAMOXIFEN 2 ys ANASTROZOLE 3 ys

TAMOXIFEN 5 ys
ITA
n=448 TAMOXIFEN 2-3 ys ANASTROZOLE 2-3 ys

GROCTA 4B TAMOXIFEN 5 ys
n=380 TAMOXIFEN 3 ys AMINOGLUTEMIDE 2 ys

All this studies employ a sequential strategy

for a total of 5 years of HT
 Femara vs. Tamoxifen
Breast International Group
(BIG) 1-98: The Femara
Adjuvant Therapy Trial

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Diseño

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Seguridad:

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 Letrozole
MA 17 Tamoxifen R
Placebo

4.5-6 ys 5 ys

Exemestane
NSABP B33 Tamoxifen R
Placebo

5 ys 5 ys

These studies evaluate the use of AIs after a

5-years course of TAM
 MA-17 is the first study to prove the
benefit of extended adjuvant therapy
after adjuvant tamoxifen in
postmenopausal women with HR+ early
breast cancer

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Recurrencias:

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Sobrevida libre de
eventos:

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Metástasis a distancia:

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Mortalidad:

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