Background

Question 1

What are the 3 most commonly diagnosed cancers in women in decreasing order of incidence?

Answer 1

Most commonly diagnosed cancers in women: breast > lung > colorectal (Siegal R et al., Cancer Stats 2017)

Question 2

What are the 3 most common causes of cancer death in women in decreasing order of incidence?

Answer 2

Most common causes of cancer death in women: lung > breast > colorectal (Siegal R et al., Cancer Stats 2017)

Question 3

Appx how many women in the United States are diagnosed with invasive and noninvasive breast cancer, and how many will die of breast cancer annually?

Answer 3

Incidence: ∼253,000 invasive breast cancers and ∼63,000 noninvasive breast cancers annually

Mortality: ∼41,000

(Siegal R, Cancer Stats 2017)

Question 4

What is the median age of Dx for invasive breast cancer?

Answer 4

The median age for invasive breast cancer is 61 yrs. (Miller et al., Cancer Treatment & Survivorship Facts & Figures 2016–2017)

Question 5

What race has the highest rate of breast cancer Dx? What race has the highest rate of breast cancer mortality?

Answer 5

Highest Dx: whites

Highest mortality: blacks

(DeSantis et al., Breast Cancer Statistics 2017)

Question 6

What percentage of women will be diagnosed with breast cancer in their lifetimes?

Answer 6

∼12% (1 in 8) of U.S. women will be diagnosed with breast cancer. (DeSantis et al., Breast Cancer Statistics 2017)

Question 7

Between 2010 and 2020, is the incidence of breast cancer in the United States expected to increase or decrease?

Answer 7

The incidence is expected to increase. (Weir et al., Cancer 2015)

Question 8

In the United States in 2015, was the incidence of breast cancer mortality increasing or decreasing?

Answer 8

The incidence of mortality was decreasing. (DeSantis et al., Breast Cancer Facts & Figures 2017–2018)

Question 9

What % of breast cancers are due to known hereditary mutations in single genes?

Answer 9

≤10% (Foulkes WD et al., NEJM 2008)

Question 10

What are the 2 most common hereditary mutations that predispose to breast cancer?

Answer 10

BRCA1 and BRCA2 are the most common mutations. (These are most common in the Ashkenazi Jewish population, where they are found in as many as 1 in 40.) (Metcalfe KA et al., JCO 2010)

Question 11

Mutations in which gene, BRCA1 or BRCA2, confers a higher risk of ovarian cancer?

Answer 11

Both BRCA1 and BRCA2 are associated with increased risk of ovarian cancer, but risks are higher with BRCA1 (45% lifetime risk) compared to BRCA2 (15% lifetime risk). (Chen S et al., JCO 2007)

Question 12

What are 2 other hereditary syndromes associated with an increased risk of breast cancer and their related germ line mutations?

Answer 12

Both are a result of mutations in tumor suppressor genes:

1. Li-Fraumeni syndrome: TP53
2. Cowden/Bannayan–Riley–Ruvalcaba syndrome: PTEN

Question 13

Is HRT with estrogen and progestin associated with an increased or decreased risk of breast cancer?

Answer 13

HRT with estrogen and progestin is associated with an increased RR of 1.7.

Question 14

Separate the following factors into those that increase or decrease the risk of breast cancer: younger age at menarche, younger age at menopause, nulliparity, prolonged breastfeeding, use of HRT.

Answer 14

Increase risk: younger age at menarche, nulliparity, use of HRT

Decrease risk: younger age at menopause, prolonged breastfeeding

Question 15

Estimate the annual risk of a contralat breast cancer in the 10 yrs following a primary Dx.

Answer 15

Premenopausal: 1%/yr

Postmenopausal: 0.5%/yr

Question 16

What is the definition of natural menopause and what is the median age at which is occurs?

Answer 16

Definition: permanent cessation of menstrual periods (12 mos of amenorrhea) without other obvious pathologic or physiologic cause.

Median age: 51 yrs

Question 17

What are the United States Preventive Services Task Force (USPSTF) screening recommendations for normal-risk women age 40–49 yrs, age 50–74 yrs, and age >74 yrs?

Answer 17

For normal-risk women age 40–49 yrs: individualized decision based on potential benefits and potential harms

For normal-risk women age 50–74 yrs: biennial mammogram

For normal-risk women age ≥74 yrs: insufficient evidence to assess balance of benefits and harms (USPSTF 2016)

Question 18

What are the ACS screening recommendations for normal-risk women age 40–44 yrs, age 45–54 yrs, and women ≥55 yrs?

Answer 18

For normal-risk women age 40–44 yrs: opportunity for annual mammogram

For normal-risk women 45–54 yrs: annual mammogram

For normal-risk women ≥55 yrs: biennial mammogram, with opportunity to continue annual mammogram (no age cutoff, as long as life expectancy is ≥10 yrs, whereas the USPSTF recommends biennial screening mammography beginning at age 50 and discontinuation at age 74.) (Oeffinger/ACS, JAMA 2015)

Question 19

For a woman with prior thoracic RT between ages 10 and 30 yrs, when should screening begin for breast cancer and how?

Answer 19

According to NCCN guidelines (2018):

Age <25: annual clinical breast exam (CBE) beginning 8–10 yrs after RT

Age ≥25: CBE every 6–12 mos + annual mammogram and breast MRI beginning 8–10 yrs after RT

Question 20

When should a woman be screened for breast cancer using MRI?

Answer 20

NCCN (2018) recommends MRI to be used as an adjunct to mammography for women with a BRCA mutation or women who are 1st-degree relatives of a BRCA carrier (but are themselves untested) beginning at age 25, women with Li-Fraumeni (TP53) syndrome and their 1st-degree relatives, women with Cowden/Bannayan–Riley–Ruvalcaba (PTEN) syndrome and their 1st-degree relatives, women with mutations in ATM, CDH1, CHEK2, PALB2, PTEN, or STK11 with an expected ≥20% lifetime risk of breast cancer, women without known genetic mutations who have a lifetime risk of ≥20% as defined by models that are highly dependent on family Hx, and women who rcvd T or CW irradiation between the ages of 10 and 30.

Question 21

According to NCCN 2018, what are the potential clinical indications and applications of dedicated breast MRI testing?

Answer 21

Breast MRIs should be performed only where there is a dedicated breast coil, an experienced radiologist, and capacity for MRI-guided Bx. Since false+ findings on MRI are common, surgical decisions should not be based solely on MRI; additional tissue sampling should be performed in areas of concern identified by MRI.

Define extent of cancer, multifocal or multicentric Dz in the ipsi breast
Screen for contralat breast cancer in a newly diagnosed breast cancer pt
Evaluate before and after neoadj therapy to define extent of Dz, response to Tx, and potential for breast conservation
Detect additional Dz in women with mammographically dense breasts
Detect primary Dz in pts with +axillary LNs or Paget Dz of the nipple when primary is not identified on mammogram, US, or physical exam

Question 22

Name the 5 rare histologic types of breast cancer that have a more favorable overall prognosis than invasive ductal/lobular carcinoma.

Answer 22

Rare types of breast cancer with a more favorable prognosis:

1. Tubular
2. Mucinous
3. Medullary (not including atypical medullary)
4. Cribriform
5. Invasive papillary

Question 23

Name the 1 rare histologic type of breast cancer that has a less favorable overall prognosis than invasive ductal/lobular carcinoma.

Answer 23

Micropapillary carcinoma has a less favorable overall prognosis.

Question 24

What is the Oncotype DX, and which breast cancer pts are eligible for its use?

Answer 24

Oncotype DX is a 21-gene assay that quantifies the likelihood of distant recurrence in tamoxifen-treated ER+, node– breast cancer patients (Paik S et al., NEJM 2004). Evaluation of Oncotype DX in pts from NSABP B20 suggests that the recurrence score also predicts the magnitude of chemo benefit (Paik S et al., JCO 2006). NCCN currently recommends considering Oncotype DX in patients with >0.5 cm, ER+, node– and N1mic pts.

Question 25

What are the 4 major molecular subtypes of breast cancer? Which subtype is associated with the poorest prognosis?

Answer 25

Molecular subtypes:

1. Luminal A (ER+/HER2–, ↓ proliferation)
2. Luminal B (ER+/HER2±, ↑ proliferation)
3. HER2 overexpressing
4. Basal-like (ER–/PgR–/HER2–)
   The basal-like subtype carries the poorest prognosis.

Question 26

What are phyllodes tumors of the breast, and what is the most important factor that determines risk of recurrence?

Answer 26

Phyllodes tumors (cystosarcoma phylloides) are rare tumors containing both stromal and epithelial elements. Although the subtypes range from benign to malignant, the most important prognostic factor for recurrence is a clear margin after resection.