Molecular categorization of breast cancer tumors has recently evolved to include

HER2-low status, with ≈46% of tumors classified as HER2-low

16,*

100

5-Year Relative Survival (%)

UnknownHR+/HER2- HR+/HER2+

HR-/HER2-

100%

90.3%

34%

99.1%

89.8%

45.6%

HR-/HER2+

97.2%

84%

39.5%

91.8%

66.2%

12.8%

96.6%

77.3%

17.8%

NUMEROUS GENES ARE LINKED

TO HEREDITARY DISEASE

≈5%-10% of all BCs are hereditary

6,17,18

≈25

While other genes have been linked to

hereditary disease, BRCA1 and BRCA2

are the most well studied

of hereditary cases are due to germline

mutations of BRCA1 and/or BRCA2

17,18

HR+/HER2- is the most common breast cancer molecular subtype

100

Breast Cancer

Overview

Represents 15% of all new cancer

cases and is the 2nd leading cause of

cancer deaths

≈30% of women with early disease will

develop advanced or metastatic disease

≈297,790 new cases of invasive disease

in 2023

2,†

63 years median age at diagnosis

Breast cancer (BC) evolves silently, often discovered

during routine screening. Abnormal cell growth

begins in the breast tissue, leading to the formation

of a tumor or mass. Tumors may spread to other

parts of the body, resulting in metastases.

BREAST CANCER IN THE US

*Excluding nonmelanoma of the skin.

†

Greater than 50% of all new cases will occur in women aged 55-74 years.

MALE

FEMALE

As of January 1, 2022, ≈4.1 million

women had a history of BC, ≈4% of

whom had metastatic disease

≈6% present with metastatic disease

at the time of 1st diagnosis

≈43,170 estimated deaths in 2023

70 years median age at death

References

1. Alkabban FM, Ferguson T. StatPearls. Breast cancer. Updated September 26, 2022. Accessed March 8, 2023. https://www.ncbi.nlm.nih.gov/books/

NBK482286/. 2. American Cancer Society. Cancer Facts & Figures 2023. American Cancer Society; 2023. 3. Giaquinto AN, et al. CA Cancer J Clin.

2022;72:524-541. 4. Breastcancer.org. Metastatic breast cancer. Accessed April 5, 2023. https://www.breastcancer.org/types/metastatic. 5. National

Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: female breast cancer. Accessed April 26, 2023.

https://seer.cancer.gov/statfacts/html/breast.html. 6. American Cancer Society. Breast Cancer Facts & Figures 2022-2024. American Cancer Society, Inc.

2022. 7. American Cancer Society. Key statistics for breast cancer in men. Accessed April 5, 2023. https://www.cancer.org/cancer/

breast-cancer-in-men/about/key-statistics.html. 8. American Cancer Society. Can breast cancer in men be found early? Accessed April 5, 2023.

https://www.cancer.org/cancer/breast-cancer-in-men/detection-diagnosis-staging/detection.html. 9. Centers for Disease Control and Prevention.

What are the risk factors for breast cancer? Accessed April 5, 2023. https://www.cdc.gov/cancer/breast/basic_info/risk_factors.htm. 10. National Cancer

Institute. Breast cancer treatment (PDQ

)–health professional version. Accessed April 5, 2023. https://www.cancer.gov/types/breast/hp/

breast-treatment-pdq. 11. American Society of Clinical Oncology. Breast cancer-metastatic: introduction. Accessed April 5, 2023.

https://www.cancer.net/cancer-types/breast-cancer-metastatic/introduction. 12. National Cancer Institute. NCI dictionaries: early-stage breast cancer.

Accessed April 5, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer. 13. National Cancer Institute.

Cancer stat facts: female breast cancer subtypes. Accessed April 26, 2023. https://seer.cancer.gov/statfacts/html/breast-subtypes.html. 14. Medscape.

Breast cancer and HER2. Accessed April 5, 2023. https://emedicine.medscape.com/article/1689966-overview. 15. National Cancer Institute. Breast

cancer treatment (adult) (PDQ

)–patient version. Accessed April 5, 2023. https://www.cancer.gov/types/breast/patient/breast-treatment-pdq.

16. Holthuis EI, et al. Breast. 2022;66:278-284. 17. Arpino G, et al. BMC Cancer. 2016;16:924. 18. Kleibl Z, Kristensen VN. Breast. 2016;28:136-144.

*Because of its rarity, breast cancer in men may be overlooked and may be diagnosed later than in women,

which can impact outcomes.

RISK FACTORS

The risk of breast cancer

increases with age

6,9

≈30% of postmenopausal cases can be attributed to excess

body weight, physical inactivity, and alcohol consumption

DCIS = ductal carcinoma in situ.

Relative risks for some factors vary by BC molecular subtype.

†

During their adulthood and/or after menopause.

MODIFIABLE

6,9

NONMODIFIABLE

6,9

REPRODUCTIVE/HORMONAL

6,9

‡

Risk increases with each number of first-degree relatives who had BC.

Inherited mutations for genes associated with BC.

6,9

Mammographically dense breasts ≥26%.

Physical inactivity

Being overweight/

obese

†

Drinking alcohol

Age (65+ years)

Family history

‡

Personal history of

breast cancer, including

DCIS or lobular

carcinoma in situ

History of benign

breast disease

Genetic mutations

Dense breast tissue

High-dose radiation to

the chest

Age at the start of menstruation (<11 years)

Reproductive history

• Age at first child (>30 years)

• Not breastfeeding

• Never having a full-term pregnancy

Hormonal factors

• Hormone replacement therapy

• Certain oral contraceptives

Menopause

• Late menopause (>55 years)

• High endogenous estrogen or

testosterone levels post menopause

STAGE AT DIAGNOSIS IS AN IMPORTANT

DETERMINANT OF SURVIVAL

Breast cancer staging involves assessment of the size of the primary tumor (T),

regional lymph node involvement (N), and distant metastasis (M)

10,11,*

Stage I Stage II Stage III Stage IV

eBC

†

aBC

‡

mBC

aBC=advanced breast cancer; eBC=early breast cancer; mBC=metastatic breast cancer.

The staging in the figure is relevant to TNM only. Other clinical factors may be included in the determination of prognostic stage (eg, histologic grade and

receptor status).

†

Early BC is breast cancer that has not spread beyond the breast or axillary lymph nodes and includes DCIS and stages I, IIA, IIB, and IIIA.

‡

Advanced BC is breast cancer that may have spread from where it first started to nearby tissue or lymph nodes and includes stages IIIB and IIIC.

10,11

Metastatic BC is breast cancer that has spread from the breast to other places in the body and includes stage IV.

10,11

Disease Presentation

at Diagnosis

5-Year Relative Survival by

Stage at Diagnosis

Localized

Confined to primary site

Regional

Spread to regional lymph nodes

Distant

Cancer has metastasized

Unknown

Unstaged

Percentage

Stage

Stage I Stage II Stage III Stage IV

>99

MAJOR MOLECULAR SUBTYPES ARE DEFINED BY

CELL RECEPTOR STATUS

Steroid hormone receptors (HR) and human epidermal growth factor 2

(HER2) expression are key molecular features of BC

10,13

Nucleus

HER2

receptor

HER2

gene

(ERBB2)

ER/PR

Estrogen

receptor-positive (ER+)

BCs have increased

estrogen receptors

• Tumors grow in response

to estrogen

Progesterone

receptor–positive (PR+)

BCs have increased

progesterone receptors

• Tumors grow in response

to progesterone

Amplification

multiple HER2 genes

Overexpression

many HER2 receptors

strogen hormones, progesterone

hormones, and growth factors can

attach to receptors, fueling cell

division and growth

Level of HER2 is increased. HER2+ cells

grow and divide faster than HER2- cells

Triple-negative breast cancer (TNBC) does not have overexpression of ER, PR, or HER2

Percentage of Cases

by Subtype

HR+/HER2- HR-/HER2-

HR+/HER2+

UnknownHR-/HER2+

*As assessed via a retrospective, population-based cohort study of 1261 women diagnosed with mBC in the Netherlands between January 1, 2008, and

December 31, 2016, for whom HER2 and HR status was known.

5-Year Relative Survival for

Breast Cancer by Stage and Subtype

HR Positive

HER2 Positive

14,15

Triple Negative

≈2800 new cases of invasive disease

in 2023

≈530 expected deaths in 2023

Most common cancer among women, with

1 in 8 being diagnosed in their lifetime

1,2,*

Rare disease accounting for <1% of all breast cancers

6,*

SUMMARY

*Excluding nonmelanoma of the skin.

Breast cancer is the most common

cancer among women and the second

most common cause of death from cancer,

following lung cancer

2,*

The risk of BC increases with age;

≈30% of postmenopausal BC cases can be

attributed to modifiable behaviors

6,9

Approximately 5%-10% of all cases are

hereditary, with BRCA1 and BRCA2

germline mutations accounting for about

one quarter of all hereditary cases

6,17,18

BC stage at diagnosis and molecular

subtype (HR and HER2 status) are

important determinants of survival

3,13

5-year survival rates are ≈30% for mBC

1 in 833 men will be diagnosed in their lifetime

TNM STAGING OF BC

IA IB

1 0–1

0 1 mi

0 0

IIA IIA/B IIB

0–1 2 3

1 0–1 0

0 0 0

IIIA IIIA IIIB IIIC

0–2 3 4 Any

2 1–2 0–2 3

0 0 0 0

Any

HR+ cellNormal cell

Nucleus

HR2+ cellNormal cell

Localized Distant

Regional

BC Classification by HER2 and HR Subtypes

100

Percentage of Total Population (N = 1261)

HER2-0

n = 373

HER2-low

n = 472

37.4%

11.4%

HER2+

n = 144

29.6%

HR+ Tumors

16,*

(n=989)

HR- Tumors

16,*

(n=272)

HER2-0

n = 110

HER2-low

n = 104

HER2+

n = 58

8.2%

4.6%

8.7%

and/or