BREAST CANCER:

INCIDENCE, RISK
FACTORS,
DIAGNOSIS AND
TREATMENT

Prof. Elona Juozaitytė

Dr. Erika Korobeinikova
LITHUANIAN UNIVERSITY OF
HEALTH SCIENCES
 BREAST CANCER INCIDENCE
 Worldwide, breast cancer is the most common type of cancer;

 2.3 million new woman breast cancer cases diagnosed in 2020

(25 % of all woman cancers).
Estimated age-standartized incidence rates in
 Breast cancer incidence is high in developed regions of the 2020, both sexes, all ages.
world and low in most developing regions.

Countries where breast cancer is the most frequently diagnosed cancer in

women, 2018

Ferlay J et al. Global Cancer Observatory: Cancer Today, 2018.

 BREAST CANCER MORTALITY
Distribution of Deaths for the Top  Breast cancer ranks as the fifth Mortality rate per 100.000 woman
10 Most Common Cancers in 2020. cause of death from cancer overall
(0.68 million deaths in 2020) and
first among woman;
Both Sexes

 Since 1990, in many European

countries, breast cancer mortality is
decreasing by 1–2% per year,
thanks to early detection and
improved treatment.

Women

GLOBOCAN 20202
 BREAST CANCER IN EUROPE

 Breast cancer accounts for 13.3% of all new cancer cases diagnosed in EU-27
countries in 2020, it accounts for 28.7% of all new cancers in women.

European commission. Breast cancer burden in EU 2020

 BREAST CANCER IN LITHUANIA

 Breast cancer ir the most common

cancer among woman in Lithuania;

 2807 new woman breast cancer cases

and 25 men breast cancer cases were
diagnosed in 2017;

 Incidence rate 184 cases/100 000

woman.

Lithuaninan Aukštaitija National Park

BREAST CANCER MANAGEMENT DIFFERENCES

 There are many national and international guidelines Similar but different
for breast cancer management (ESMO, DKG
(German), NICE (UK), SCR (Swedish), the French
Breast Cancer Intergroup, etc.) with quite significant
discrepancies;

 It has been reported that in Europe there were still

wide differences in treatment offered to patients with
breast cancer in terms of mastectomy and
radiotherapy rates and use of adjuvant chemotherapy
and hormone therapy;

 It has also been shown that the specialized Van Gogh vs. Chuck Norris
multidisciplinary breast cancer care was associated
with a significant reduction in mortality.

Wilde et al.; 2020

Rosselli Del Turco et all. European journal of cancer; 2010
 WHY BREAST CANCER INCIDENCE IS GROWING?
 Growing incidence of breast cancer is associated
with endogenous and exogenous ovarian
hormone exposure, reproductive factors, diet
and life style;
Estimated number of new woman breast cancer
cases from 2020 to 2040 (WHO world countries)

 Age, family history, and both endogenous and

exogenous ovarian hormone exposure have an
important effect on risk and have been
incorporated into models that predict individual
risk of breast cancer;

 Diet, alcochol use and other factors play a

smaller role;

 Inherited mutations in BRCA1, BRCA2 play a role

in the development of breast cancer and can be
directly tested in individuals.
M.D. Abeloff’s Clinical Oncology
 BREAST CANCER RISK FACTORS I
Age Incidence rates are substantially higher for
women age 50 and older.
Sex Approximately 1% of breast cancers occur in IN EUROPE:
males.

Endogenous Earlier age of menarche (<12 year old), later

hormones age of menopause (>55 year old), nulliparity
or late age of first birth (>30 year old) short
breast feeding, all of which determine the
cumulative number of ovarian cycles.

Exogenous Oral contraceptive usage. Risk is higher if

hormones contraceptives are used at young age
(<18year old) or long period (>10 years).
Estrogen hormone replacement therapy for
postmenopausal women is associated with
small but significant risk of invasive breast
cancer.
Hortogagyi et al. Clin Breast Cancer2005; Fentiman IS et al. Lancet 2006 European commission. Breast cancer burden in EU 2020
 BREAST CANCER RISK FACTORS II

Diet Association between body mass index and breast cancer. Alcohol
consumption is the best established dietary factor associated with
increased risk for breast cancer.

Ionizing The knowledge about radiation-related breast cancer risk in women

radiation derives from epidemiological studies of patients exposed to
diagnostic or therapeutic radiation and of the Japanese atomic
bomb survivors.

Family Breast cancer is approx. twice as common among first-degree

history relatives of breast cancer patients. The two most important breast
cancer susceptibility genes, BRCA1 and BRCA2, were identified by
linkage analyses in 1990.

Zhang SM J Nat Cancer Inst,2003; Touilland MS J Nat Cancer Inst,2007; Tworoger SS J Clin Oncol 2007; Wooster R N Engl J Med 2003
 FAMILY HISTORY AND BREAST CANCER RISK
Incensement in breast cancer relative risk if the first-degree
female relative (sister, mother, daughter) had breast cancer:
Mother, daughter or sister Reliative risk

Diagnosed with breast cancer in

3,0
premenopausal status

Diagnosed with bilateral breast

5,0
cancer

Diagnosed with bilateral breast

9,0
cancer in premenopausal status

Diagnosed with breast cancer in

1,5
postmenopausal status
HEREDITARY BREAST-OVARIAN CANCER SYNDROME

 BRCA gene mutations

can explain 10-15%
breast cancer cases;
 About 0.2% of
population have BRCA
mutations;
 Breast cancer can
occur at individuals
having no mutations.

Breast link. Breast Cancer 101; 2020

SEVERAL RISK FACTORS SUM UP
RISK FACTORS ARE CHANGING

• Industrial cancerogens;
• Environmental pollution.

BUT:

• Marriages are postponed to later time due carrier;

development – baby deliveries are late;
• Baby breast feeding short;
• Women use food supplements more frequently
comparing to men.
 BREAST CANCER SCREENING

 Biannual mammography screening has been

shown to have the greatest effect on the breast
cancer mortality reduction among women aged
50-69 years;

 Recommended by the European Union;

 American Cancer Society suggested screening

guidelines – yearly mammograms are
recommended starting at age of 40 years.

Tabar et al. Cancer, 2018; American Cancer Society Recommendations for the Early Detection of Breast Cancer, 2021;
 ADDITIONAL SCREENING RECOMMENDATIONS

American Cancer Society guidelines: BREAST SELF-EXAM

 Self examination (low sensitivity and specificity, cancer may
be diagnosed earlier, does not decrease mortality risk) -
women should know how their breasts normally feel and
report any breast changes promptly to their health care
providers. Breast self-exam is an option for women starting
in their 20s;

 Women at increased risk (e.g., family history, genetic

tendency, past breast cancer) should talk with their doctors
about the benefits and limitations of starting mammography
screening earlier, having additional tests (i.e., breast
ultrasound and MRI), or having more frequent exams.

 Clinical breast exam (sensitivity 45-87%, specificity depends

on experience, value is low) - should be part of a periodic
health exam, about every three years for women in their 20s
and 30s, and every year for women 40 and older.
American Cancer Society Recommendations for the Early Detection of Breast Cancer, 2021; Breast Cancer Welfare Association Malaysia (BCWA), 2020.
BREAST CANCER FORMATION
 Normal tissues

 Ca in situ

 Invasive cancer

 Metastases
 BREAST CANCER DIAGNOSIS

 Diagnosis and treatment should be

performed at specialised “Breast units” that
care for a high volume of breast cancer
patients;

 Care should be provided by a

multidisciplinary team including surgeon,
radiation oncologist, medical oncologist,
radiologist, pathologist - all specialised in
breast cancer.

Barba et al. Critical reviews in oncology/hematology, 2021.

BREAST CANCER DIAGNOSTIC EXAMINATIONS I
Clinical examination:

 Medical history, including family cancer

history and menopausal status;

 Physical examination, including palpation

of the breasts and locoregional lymph
nodes;

 Evaluation of Performance status,

comorbidities;

Laboratory assessments:

 Full blood count;

 Liver and renal function tests;
 Etc.
 BREAST CANCER DIAGNOSTIC EXAMINATIONS II
Radiological examination: mammography
 Mammography is the main screening method and very sensitive method in detecting occult
malignancy in postmenopausal patients when breast tissue is replaced with fat.
 Sensitivity <50y – 60%, >50y – 80%. Specificity 94-99%.
 May detect lesions as small as 2mm and reveal cancer 2 year earlier than clinical examination.

Signs of breast cancer in mammogram:

Spiculated mass Calcifications Bilateral asymmetry

Kowsalya et al. 2016.
BREAST CANCER DIAGNOSTIC EXAMINATIONS III
Radiological examination: breast ultrasonography

Signs of breast cancer in ultrasonography:  Irregular, hypoechoic mass;

 Indistinct, spiculated margin
 Echogenic halo
 Posterior shadowing
 Architectural distortion of the
surrounding tissue

 Ultrasonography is more informative for

premenopausal patients. Performed for all
suspected breast cancer patients due to
additional information it gives about lump
size and lymph node involvement;
Invasive ductal carcinoma in a 72 year old patient.

Wojocinski et al. BMC Women’s health, 2013.

BREAST CANCER DIAGNOSTIC EXAMINATIONS IV
Radiological examination: breast magnetic resonance immaging

 MRI may be considered in certain cases:

familial breast cancer associated with BRCA
mutations. Cases where conventional
imaging results are inconclusive.
 BREAST CANCER DIAGNOSTIC EXAMINATIONS V
Radiological examination: assessment of distant metastases

 Additional imaging is indicated only if there are signs

and symptoms of metastatic disease.
 Tests may include:
 Chest diagnostic CT with contrast;
 Abdominal/pelvic dagnostic CT with contrast or MRI
with contrast;
 Brain MRI with contrast if suspicious CNS symptoms;
 Spine MRI with contrast if back pain or symptoms of
cord compression;
 Bone scan or sodium fluoride PET/CT
 FDG PET/CT (optional)
 Other.

NCCN Guidelines version 5.2021; National breast cancer foundation.

 BREAST CANCER DIAGNOSTIC EXAMINATIONS VI
Pathological examination: biopsy

Core needle biopsy before any type of treatment, obtained

preferably using ultrasound or stereotactic guidance, or using
manual guidance, providing information on:

 Histological type and grade;

 Estrogen receptor (ER), Progesteron receptor (PR) and

human epidermal growth factor receptor 2 (HER2) status;

 Proliferation markers (Ki67);

 For the purpose of prognostication and treatment

decision-making, tumors are grouped into surrogate
intristic subtypes defined by routine histology and
immunohistochemistry (IHC) data.
SingHealth. Breast Cancer - Diagnosis to Treatment, 2019.
 BREAST CANCER HISTOLOGICAL TYPES

Malhotraet al.2010
 BREAST CANCER MOLECULAR SUBTYPES

Sasmita et al. 2018

PROGNOSIS OF DIFFERENT MOLECULAR SUBTYPES
Frequency: Subtype 5y local relapse 5y distant metastases

Luminal A 0,8 % 3,3%

Luminal B 1,5 % 12%
HER2 8,4 % 19%
Basal/triple negative 7,1 % 16%

Nguyen, et al ICO2008:26 2373

TNM STAGING SYSTEM: T STAGE
TNM STAGING SYSTEM: N STAGE
 TNM STAGING SYSTEM: M STAGE

 MX- Distant metastasis cannot be assesed; Most common sites of metastases:

5-1o%
 M0- No distant metastases;

 M1 - Distant metastases.
15-25%

Approximatly 75 percent of 5-15%

metastases occur within the first 5
years after the diagnosis of early
stage disease, especially among
patients with HR negative disease. 20-60%
 PROGNOSTIC AND PREDICTIVE FACTORS

PROGNOSTIC FACTOR PREDICTIVE FACTOR

Who? needs the treatment Which? treatment is best

“A prognostic factor is a measurable “Predictive factor is any measurable

clinical or biological characteristic characteristic associated with a response
associated with a disease-free or overall or lack of a response to a specific
survival period in the absence of treatment.”
adjuvant therapy.”

Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol.2007;608:1-22
 PROGNOSTIC FACTORS
TUMOUR ASSOCIATED PATIENT ASSOCIATED
 Stage of the disease  Age
 Number of involved lymph nodes  Menopausal status
 Tumor size  Family history
 Differentiation of the tumor  Performance status
 Mitotic activity
 Vascular invasion
 ER/PR status
 HER-2/neu statuss
 Proliferation markers (Ki67)
 P53 mutation
 Bone marrow invasion.
 PREDICTIVE FACTORS
FACTOR PREDICTION

ER status Predicts tumor response to endocrine

therapy. Much higher response if ER
positive.
PR status Predicts tumor response to endocrine
therapy. Higher response if PR
positive.
HER2 status Predicts tumor response to antiHER2
therapy. Higher response if HER2
positive.
Ki67 Predicts tumor response to
chemotherapy.
Higher response if Ki67 is high.
Oncotype DX, Predicts tumor response to
32
Cianfrocca and Goldstein. Oncologist. 2004;9(6):606-616; Lonning PE. Ann Oncol. 2007 chemotherapy
 GENE EXPRESSION PROFILES

 Gene expression profiles

may provide additional
prognostic and /or
predictive information to
complement pathological
assessment and to predict
response to adjuvant
chemotherapy, particularly
in patients with ER-
positive early breast cancer

 Prognostic gene expression

profiles: OncotypeDx,
Mammaprint, Prosigna,
EndoPredict and others.
CHANGES IN ROUTINE BIOMARKERS OVER TIME
 BREAST CANCER TREATMENT
 Breast cancer treatment is a compex of surgery, radiotherapy, chemotherapy, hormonal treatment
and targeted therapies.
BREAST CANCER TREATMENT STRATEGY
The treatment strategy should be based on:

 Tumor extent/location;

 Biology (pathology including biomarkers,

gene expression);

 Age and general health status of the patient;

 Possible fertility issues, including fertility-

preservation techniques, should be discussed
in premenopausal women prior to treatment
initiation.
 BREAST CANCER SURGERY
Breast cancer surgery techniques:

 Breast conserving surgery and sentinel lymph node biopsy are associated with less morbidity.

Treatmentpossible.com
 BREAST CANCER ONCOPLASTIC SURGERY
 Oncoplastic
procedures can
achieve better
cosmetic outcoms
 BREAST CANCER RADIATION THERAPY

 After breast conservation surgery whole breast

radiotherapy reduces the risk of local recurrence by
two-thirds and is associated with a survival benefit;

 Post-mastectomy radiotherapy is recommended for

women with positive deep margin, more than 4
positive axillary nodes and for those with T3-T4
tumors, independent of nodal status.
BREAST CANCER SYSTEMIC TREATMENT STRATEGY
Endocrine responsive
/non responsive
HER2 overexpressed
/HER2 negative

Comorbidities

Patient consent
 BREAST CANCER SYSTEMIC TREATMENT

 Chemotherapy:

 Neoadjuvant;

 Adjuvant;

 Chemotherapy for metastatic breast cancer.

 Hormonal therapy

 Targeted therapy
 BREAST CANCER HORMONAL THERAPY

 Endocrine therapy is only recommended for HR positive tumor

treatment;
 About 70% of breast tumors are HR positive:
 50-60% - ER(+)
 40-50% - PR(+)
 If ER(+), response to endocrine therapy is up to 60%;
 If PR(+), response to endocrine therapy is up to 30%;
 If both ER(+) and PR(+), response to endocrine therapy is up to
75%;

 Optimal endocrine treatment duration is 5 or more years.

 PERSONALISED MEDICINE

 Surrogate intrinsic tumor phenotypes, based on biomarker expression (ER,

PR, HER2 and Ki67) are the basis for treatment individualization.
PRIMARY BREAST CANCER TREATMENT DECISION
Biomarker Prognostic Predictive Test and scoring Patient selection
recommendations

ER ++ +++ IHC Hormonal treatment

(immunohistochemistry)

PR ++ + IHC If negative, chemotherapy in

some cases

HER2 ++ +++ IHC ≥10% cell (+) Anti-HER2 treatment

Ki67 ++ + IHC no consensus Chemotherapy if elevated

Intrinsic ++ ++ Gene expression profile Different response to

subtypes chemotherapy.
Chemotherapy if high risk
 CASE STUDY PRESENTATION
 A 55-year-old post-menopausal woman presents with an infiltrating
ductal carcinoma:
 Tumor size 1 cm

 ER/PR positive

 HER2 negative

 Sentinel lymph node negative

 Excellent overall health

How should this patient be evaluated for treatment?
What is her risk of disease recurrence?
How likely is she to benefit from hormonal or chemotherapy?
45
 BREAST CANCER SURVIVAL

 Survival depends on early diagnosis and stage of the

disease
 5 year cancer specific survival of breast cancer
patients:
 I stage: 98–100%
 II stage: 90-99%
 III stage: 66-98%
 IV stage: 22-28%

Weiss et al. JAMA oncology, 2018; American Cancer Society. Cancer Facts & Figures 2021.
 BREAST CANCER SURVIVAL
60 years of survival outcomes from the university of Texas MD Anderson cancer:
 BREAST CANCER FOLLOW-UP
 Monitoring of the disease depends on prognostic factors.

 Monitoring scheme:

 First 3 years – every 3 months;

 Till 5 year – every 4-6 months;

 Till 10 years – once a year.

 Methods:

 Palpation of breast, lymph nodes;

 Chest X-ray;

 Mamography every year;

 Ultrasonography or CT of abdomen;

 Sceletal scintigraphy.
 CONCLUSIONS

 Around the world, there are large variations in incidence, mortality, and
survival, and these may be due to several underlying complex factors
including ethnicity, life-style, early diagnostics, treatment availability, etc;

 In order to provide breast cancer healthcare quality assurance the national

guidelines, based on a review of the evidence based data, must be
performed.
THANK YOU