This document discusses breast cancer screening and provides guidance on screening strategies based on risk level. It covers: 1) Screening modalities like mammography, ultrasound, MRI and their limitations. Mammography is the primary screening tool for average risk women aged 50-74. 2) Risk assessment factors like family history, genetic mutations, breast density, reproductive history which determine screening frequency and additional tests. Women at high risk start screening earlier and more frequently. 3) Two case studies where mammography limitations are demonstrated. Early detection through clinical exams and additional tests led to cancer diagnosis in both cases. Regular screening tailored to risk level can improve early detection.

1. Breast Cancer Screening
IC of Family Medicine: Chan Hio Tong
Tutor: Luís Manuel Rosado de Sousa
2021/04/30

2. Breast cancer in Macau
2018 ANNUAL REPORT OF MACAO CANCER REGISTRY by Serviços de Saúde do Governo de Região Administrativa Especial de Macau

3. Breast cancer in Macau
2018 ANNUAL REPORT OF MACAO CANCER REGISTRY by Serviços de Saúde do Governo de Região Administrativa Especial de Macau

4. Breast cancer in Macau
2018 ANNUAL REPORT OF MACAO CANCER REGISTRY by Serviços de Saúde do Governo de Região Administrativa Especial de Macau

5. Content
01. What is screening?
02. Risk assessment
03. Screening modalities
04. Screening strategies
05. Case sharing

6. What is screening?
01

7. Aim of screening
General principle
Screening is of greatest value for individuals who are most likely to develop a certain disease.
For such patients, early treatment is more effective than later treatment in reducing mortality.
It is important to determine a person’s risk of developing breast cancer and use that information to:
1. Recommend the modality
2. frequency of screening
3. Determine whether referrals are needed for genetic testing /chemoprevention / prophylactic surgery.

8. Harms of screening
• Anxiety produced by false-positive screening test
• Harms with diagnostic testing after a positive screening test
• Treated overdiagnosis condition which would never become clinically apparent
• Overtreatment of some tumors that would never became apparent
• Economic cost: healthcare system/patient
Comorbid condition may decrease benefits of screening and increase the harm.

9. Screening method
Populational screening
Questionnaire based
Opportunistic screening
Screening method and frequency depends on patient’s risk assessment and physician consultation

10. Risk assessment
02

11. Risk factors for breast cancer
Obesity
Postmenopausal
Age, female, white race,
family history, genetic alternation,
breast atypia, dense breast tissue
Chest radiation history
Non-modifiable
Early menarche
Late first pregnancy >35 years old
Absence of breastfeeding
Nulliparity
Reproductive factor
Alcohol
Current smoking
Substance use
Combined estrogen-progesterone in
women with intact uteri
Hormone therapy

12. Risk factors for breast cancer

13. Probability% of developing breast cancer by Age
Data from United States, 2015 to 2017
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. doi:10.3322/caac.21654

14. Genetic mutation
Specific genetic mutations that predispose to breast cancer are rare.
Only 5-6%of all breast cancers are directly attributable to inheritance of genetic mutations.
BRCA1, BRCA2, p53, STK11, CDH1, PALB2, PTEN and the mismatch repair genes.
In BRCA1/2, pathogenic variants in these genes are implicated in about
15% of women with familial breast cancer.

15. BRCA1 and BRCA2
Meta-analysis
Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25:1329.
Breast cancer risk at 70 years old was 57% for BRCA1, 49% for BRCA2.
BRCA1 BRCA2
←57%
←49%

16. Protective or non-influence factors
Protective factors/lower risk
Higher BMI in premenopausal
Low-fat dietary pattern in postmenopausal
Regular moderate physical activity Non-influence factors
Single estrogen replacement with prior
hysterectomy
Abortion, caffeine intake, in vitro
fertilization, cosmetic breast implants,
and hair dyes

17. Lifetime risk being diagnosed for breast cancer
There is no standardization or consensus about the exact percentages of lifetime risk of developing breast
cancer within each risk category, generally they are as follows:
There is less than 15% risk of developing
breast cancer in a lifetime.
Average risk
There is 15-20% risk of
developing breast cancer in a
lifetime.
Moderate risk
There is >20% risk of
developing breast cancer in a
lifetime.
High risk
>20%
<80%
<15%
>85%
15-
20%
80-85%
Howlader N, Noone AM, Krapcho M, et. al. (eds). SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD, 2012. Retrieved September 7, 2012.

18. Non-dense breast tissue
Average risk
Untested first-degree relatives of BRCA mutation carrier / chest radiation at age 10-30
High risk
Dense breast tissue / Personal history of breast cancer / Previous biopsy resulting in lobular
neoplasia / atypical ductal hyperplasia
Moderate risk
Risk category
BRCA1 and BRCA2 mutation carrier / Genetic syndrome mutation carrier
Very high risk

19. Gail model
https://bcrisktool.cancer.gov/

20. Screening modalities
03

21. Mammography
• Mammography is the best-studied imaging technique and proved in multiple randomized trials.
• Sensitivity of mammography is inversely correlated with breast density. Mammography is less
sensitive in younger than older women.
Category Management
Likelihood of
malignancy
BI-RADS 0 Incomplete Recall for additional imaging N/A
BI-RADS 1 Negative Routine mammography screening 0%
BI-RADS 2 Benign Routine mammography screening 0%
BI-RADS 3 Probably benign
Short interval (6 month) follow up or
continued surveillance mammography
0-2%
BI-RADS 4
4a Low suspicious
Tissue diagnosis
2-10%
4b Moderate suspicious 11-50%
4c High suspicious 51-95%
BI-RADS 5 Highly suggestive of malignancy Tissue diagnosis >95%
BI-RADS 6 Known biopsy-proven malignancy Surgical excision N/A

22. Ultrasound
• not typically used in the routine screening
• may detect additional early-stage breast
cancers that are mammographically occult,
particularly in those with dense breast tissue
• the additional screening test carries a
substantial risk for false-positive results.

23. Magnetic resonance imaging
• There are no data from randomized trials that show a benefit of screening by magnetic resonance
imaging (MRI) in women at average risk for breast cancer.
• MRI for detecting breast cancer requires injection of intravenous contrast material and costs
substantially more than mammography.

24. Breast self examination
 Benefit
• Education about self-awareness
• General breast health
• WHO recommends BSE as a way to
empower women and raise
awareness among women at risk
• Lower risk of death or metastasis
• Lesser advanced stage cancer
 Harm
• Gain anxiety if found abnormality
• False positive result
Harvey BJ, Miller AB, Baines CJ, Corey PN. Effect of breast self-examination techniques on the risk of death from breast cancer. CMAJ 1997; 157:1205.
Newcomb PA, Weiss NS, Storer BE, et al. Breast self-examination in relation to the occurrence of advanced breast cancer. J Natl Cancer Inst 1991; 83:260.

25. Clinical breast examination
A. Inspection
• Arms relaxed
• Arms over head
• Hands on hips
B. Axillary nodes
C. Seated breast examination
D. Supine breast examination
• Entire breast
• Chose one technique
• Circular motion with 3 different pressure
• Each breast at least 3 minutes
Sensitivity: CBE<Mammography
CBE detected ~5 % of cancers that were not visible on
mammography
Bobo JK, Lee NC, Thames SF. Findings from 752,081 clinical breast examinations reported to a national screening program from 1995 through 1998. J Natl Cancer Inst 2000; 92:971.

26. Screening Strategies
04

27. In women aged 35 to 39 years who screen with mammography, the positive predictive
value was only 1.3%, cancer detect rate was 0.16%.
No guidelines recommend routine screening
<40
Age
If any substantial concerns about breast cancer and is willing to accept the possibility of
either a false-positive result or overdiagnosis and the resulting evaluation and treatment.
Shared decision-making
40-49
Age
Every one to two years depending on an individual woman’s risk factors and preference.
All the guidelines recommend routine screening
50-74
Age
Consideration include life expectancy, risk of dying of cancer, and the number needed to
screen over the remaining lifetime to prevent cancer death
If life expectancy is at least 10 years
>75
Age
Screening in average risk
Yankaskas BC, Haneuse S, Kapp JM, et al. Performance of first mammography examination in women younger than 40 years. J Natl Cancer Inst 2010; 102:692.

28. Worldwide screening recommendation
1) World Health Organization. WHO Position Paper on Mammography Screening. World Health Organization, Geneva 2014.
2) Canadian Cancer Society. Screening for breast cancer. Screening mammography. http://www.cancer.ca/en/cancer-information/cancer-type/breast/screening/?region=on. Accessed 16 Feb 2017.
3) Oeffinger KC, Fontham ET, Etzioni R, et al. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA 2015; 314:1599.
4) Siu AL. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2016; 164:279.
5) Australian Government Department of Health. About breast screening. BreastScreen Australia Program. Published March 2015. Accessed 16 Feb 2017.
The absolute risks of breast
cancer occurrence and death for
women ages 45 to 49 are more
similar to those for women ages
50 to 54 than ages 40 to 44.
ACS considers screening
outweighs the higher false-
positive mammogram rates in
ages 45 to50.
Annual screening in 45-55

29. Moderate risk
Women with dense breast tissue, risk between 15 and 20%
Recommendation: mammography preferably with digital technique, annually starting at 40 years of age
Ultrasonography: may be appropriate
Women with personal history of breast cancer
Women with previous biopsy resulting in lobular neoplasia or atypical ductal hyperplasiaa
Recommendation: mammography preferably with digital technique annually from diagnosis
Ultrasonography: may be appropriate
MRI complementary to mammography: usually appropriate

30. High-Very high risk
BRCA1 and BRCA2 mutations carriers, untested first-degree relatives of BRCA mutation carrier
History of chest irradiation received between the ages of 10 and 30 years and genetic
syndrome mutation carriers
Recommendation: mammography preferably with digital technique, annually starting at the age of 30 years
or 10 years before the age that the first-degree relative had breast cancer, or 8 years after the irradiation in
the thorax, but not before 30 years old
Mammography and MRI: ought be performed in these patients, being complementary (non-excluding) tests

31. Case sharing
05

32. 57 year-old female
C.C. found left breast nodule by herself since 2013.
Regular follow up in HC.
Menarche at 16y/o, G3P2, age of first labor at 23y/o, Menopause since 54y/o.
Past history: HTN, DM, dyslipidemia, fatty liver.
Family history: denied history of breast cancer.
Mammography + Ultrasound: 2013(Fibroadenoma, BI-RADS 3), 2018(Fibroadenoma, BI-RADS 2).
Breast ultrasound: 2014(Fibroadenoma, BI-RADS 3)
Latest Mammography in 2021/01 reported no evidence of malignancy (BI-RADS 3)
Case 1

33. Inner
Lateral
R L
Mammography 2021/01/15
There are scattered areas of
fibroglandular density.
There is no focal asymmetry, mass,
suspicious calcification or
architectural distortion.
The skin and nipples are normal.
There are no enlarged lymph nodes
in the axillae.
Impression:
No evidence of malignancy.
BI-RADS 2
Case 1

34. However, patient found the nodule increase in size with pain then consult KWH.
Breast ultrasound on 2021/03/24: one 2cm hypoechoic nodule on left breast, consider carcinoma with
left axillary lymph node metastasis.
PET CT on 2021/04/02: consider left breast carcinoma(2.0cm*1.1cm*2.0cm) with left axillary lymph node
metastasis.
Biopsy of right breast nodule on 2021/03: INVASIVE LOBULAR CARCINOMA with ipsilateral axilla
metastasis
Conclusion
Mammography has lower sensitivity in dense breast tissue
Case 1

35. 58 years-old female
C.C. found right breast mass by herself since 2019
1st consult general surgeon since 09/2020.
Past history: Hormone replacement therapy (Estrogen+Progesterone) for pre-
menopausal symptoms since 02/2012.
Menarche at 13y/o, G2P2, age of first labor at 32y/o.
Family history: denied history of breast cancer.
Mammography: 2013(BI-RADS 1), 2018(BI-RADS 1).
Breast ultrasound: 2016(BI-RADS 2)
Case 2

36. Mammography+Ultrasound on 11/2020:
Dense breast tissue, a 0.7cmx1.3cm oval, parallel, circumscribed, hypoechoic nodule with no posterior acoustic features in the
right breast 3:00. Vascularity is not present within the lesion.
Impression: Right breast nodule, fibroadenoma is first impression. BI-RADs 3
Case 2

37. However…
Physical examination found the 1.5cm mass was ill-defined with hardness in central/lower inner
quadrant or right breast. Clinically suspicious of malignancy.
Biopsy of right breast nodule on 02/2021: Right breast INVASIVE CARCINOMA
Conclusion
Clinical examination is always the main part of the consultation
Case 2