breast cancer board Flashcards
1
Q
What is the average woman’s lifetime risk of developing breast cancer?
A
12.3%
2
Q
According to National Comprehensive Cancer Network (NCCN) guidelines, what six groups of women are considered at increased risk of breast cancer?
A
- Women who have previously received therapeutic thoracic irradiation or mantle irradiation.
- Women 35 years or older with a 5-year risk of invasive breast carcinoma, ≥1.7% based on Gail model.
- Women with a lifetime risk of breast cancer, >20% based on models largely dependent on family history, that is, BRCAPro statistical model, and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA).
- Women with a strong family history or genetic predisposition.
- Women with lobular carcinoma in situ (LCIS) or atypical hyperplasia.
- Women with a history of breast cancer.
3
Q
What is the modified Gail model?
A
A model that calculates 5-year and lifetime projected probabilities of developing invasive breast cancer
4
Q
What criteria is the modified Gail model based on?
A
- age
- age at menarche
- age at first live birth or nulliparity
- number of first-degree relatives with breast cancer 5. number of previous benign breast biopsies
- atypical hyperplasia in a previous breast biopsy
- race
5
Q
When should someone be referred for cancer genetic counseling?
A
Patients who have a personal history or close family history with any of the following criteria:
1. Early onset breast cancer, ≤50 years.
2. Two breast cancer primaries in a single individual or two or more breast cancer primaries diagnosed from the same side of the family (maternal or paternal).
3. Breast and ovarian/fallopian tube/peritoneal cancer in a single individual or from the same side of the family.
4. A combination of breast cancer with one or more of the following: thyroid cancer, pancreatic cancer, brain
tumor, diffuse gastric cancer, dermatologic manifestations of Cowden syndrome, or leukemia/lymphoma.
5. Member of family with a known mutation in a breast cancer susceptibility gene or a member of a population at risk.
6. Male breast cancer.
7. Ovarian/fallopian tube/primary peritoneal cancer.
6
Q
What is the lifetime risk of developing breast cancer in women with a BRCA-1 or BRCA-2 mutation?
A
40% to 80%
7
Q
What is the risk of developing breast cancer in women with history of LCIS?
A
10% to 20% risk for subsequent development of cancer in either breast over the next 15 years
8
Q
For women at normal risk between the ages of 20 and 39, how often should clinical breast examination be performed?
A
1 to 3 years
9
Q
For women at normal risk aged 40 years and older, how often should clinical breast examination be performed?
A
1 year
10
Q
For women at normal risk aged 40 years and older, when and how often should screening mammography be performed?
A
Annual mammogram beginning at age 40 (based on the American Cancer Society guidelines 2010, and supported by the American College of Surgeons)
11
Q
How often should women who have received prior thoracic irradiation be screened?
A
- Age <25, annual clinical breast examination.
- Age ≥25, annual mammogram and clinical breast examination every 6 to 12 months.
∗Annual mammogram should occur 8 to 10 years after radiation exposure or at age 25, whichever occurs first.
†Annual breast magnetic resonance imaging (MRI) can be considered; however, data are lacking in this cohort of women.
12
Q
What are the screening guidelines for women with a 5-year risk of invasive breast cancer ≥1.7%, based on
the Gail model?
A
Age ≥35, annual mammogram and clinical breast examination every 6 to 12 months
13
Q
What are the screening guidelines for women with a genetic predisposition to breast cancer?
A
Clinical breast examination every 6 to 12 months and annual mammogram starting at age 25, or 10 years before the youngest breast cancer case in the family. In addition, annual breast MRI is recommended as an adjunct form in women ≥25 years of age.
14
Q
What are the screening guidelines for women with a history of LCIS or atypical hyperplasia?
A
Following diagnosis of LCIS or atypical hyperplasia, annual mammogram and clinical breast examination every
6 to 12 months are recommended. Annual MRI may be considered in patients with a history of LCIS
15
Q
What is the overall sensitivity of screening mammography?
A
Approximately 75% (according to the NCCN guidelines 2010)
16
Q
For screening mammography, what is the Breast Imaging Reporting and Data System (BI-RADS) categorization?
A
Category 0: Incomplete assessment. Needs additional imaging evaluation and/or prior mammograms for comparison
Category 1: Negative
Category 2: Benign findings
Category 3: Probably benign findings
Category 4: Suspicious abnormality—biopsy should be considered
Category 5: Highly suggestive of malignancy—appropriate action should be taken Category 6: Known biopsy-proven malignancy—appropriate action should be taken
17
Q
For a Category 3 lesion, what is the likelihood of malignancy?
A
≤2%
18
Q
For a Category 5 lesion, what is the likelihood of malignancy?
A
≥95%
19
Q
What is the sensitivity of MRI in detecting breast cancer?
A
Sensitivity approximately 71% to 100%
20
Q
When is annual MRI recommended in breast cancer screening?
A
- Women with genetic predisposition for breast cancer who are ≥25 years of age.
- Women with previous diagnosis of LCIS or atypical hyperplasia.
- Women with a ≥20% lifetime risk of developing breast cancer as defined by models based largely on family history, that is, BRCAPro and BOADICEA.
- Consider in women with history of chest irradiation
21
Q
What is the difference between a screening mammogram and a diagnostic mammogram?
A
A diagnostic mammogram is performed when there are positive clinical findings. The diagnostic mammogram includes spot compression and magnification views
22
Q
Does breast ultrasound detect most microcalcifications?
A
no
23
Q
How does fibrocystic disease typically present?
A
Premenstrual cyclical mastalgia
24
Q
What is fibrocystic disease?
A
A spectrum of clinical, mammographic, and histological findings, present in 90% of women, representing an abnormal tissue response to circulating hormones
25
How does fibrocystic disease appear mammographically?
Bilateral symmetrical diffuse or focally dense tissue
26
Does presence of fibrocystic disease increase a woman’s risk of developing breast cancer?
No
27
What is a galactocele, and how is it treated?
A milk-filled cyst that typically presents during or after cessation of breast-feeding. Treatment involves aspiration or
operative excision
28
What is the treatment of a palpable cyst? How often does intracystic carcinoma occur?
Aspiration. Approximately 0.1%
29
What is Mondor disease?
A benign disorder characterized by thrombophlebitis of the breast
30
What is a fibroadenoma?
A benign tumor consisting of stromal and epithelial elements. These tumors are estrogen sensitive.
31
What is the most common solid tumor found in women younger than 30 years?
Fibroadenoma
32
How do fibroadenomas present clinically?
A solid, firm, mobile mass.
33
What is the treatment of a typical fibroadenoma?
Excisional biopsy or observation
34
What is a giant fibroadenoma?
A fibroadenoma that attains a size of greater than 5 cm in greatest dimension
35
What is the typical history of a giant fibroadenoma?
A rapidly enlarging mass in the breast of a young adult or adolescent.
36
What is an intraductal papilloma?
A true polyp of epithelium-lined breast ducts.
37
What is the typical presentation of an intraductal papilloma?
Bloody nipple discharge
38
What is the treatment for an intraductal papilloma?
Excisional biopsy. Excision is required because approximately 20% of core needle biopsy diagnosed intraductal
papillomas have been shown to be associated with malignancy.
39
What is the typical history of a patient presenting with a phyllodes tumor?
Rapidly enlarging painless breast mass
40
What is the mean age of presentation for a phyllodes tumor?
40 years, older than a patient with a fibroadenoma, but younger than a patient with invasive breast cancer.
41
Histologically, what is the makeup of a phyllodes tumor?
Composed of both stromal and epithelial elements.
42
What are the subtypes of a phyllodes tumor?
1. benign
2. borderline 3. malignant
43
What is the appropriate treatment for a phyllodes tumor?
Local surgical excision with margins 1 cm or greater.
44
When is total mastectomy indicated?
When a negative margin cannot be obtained with lumpectomy or partial mastectomy.
45
Is axillary lymph node dissection indicated in the treatment of phyllodes tumor?
No, phyllodes tumors rarely metastasize to the axillary lymph nodes. Therefore, node dissection is not indicated
(see Figure 21-1).
46
In patients who experience local recurrence, what is the recommended treatment?
Re-excision with tumor-free margins of 1 cm. Radiation therapy is controversial in the treatment of phyllodes tumors. In certain cases with more aggressive pathology, radiation therapy may be indicated.
47
Is systemic therapy using endocrine or cytotoxic agents indicated in the treatment of phyllodes tumors?
no
48
Following recommended workup including history and physical examination (H&P), diagnostic bilateral mammography, and pathology review, what is the recommended treatment for LCIS?
Observation.
49
What is the risk of developing an invasive breast cancer once diagnosed with LCIS?
Approximately 10% to 20% risk for subsequent development of cancer in either breast over the next 15 years.
50
True or False. The risk of invasive breast cancer after the diagnosis of LCIS is equal in both breasts.
True.
51
In a woman diagnosed with LCIS who wishes to undergo risk reduction surgery, what is the appropriate management?
Bilateral mastectomy
52
Do women with a diagnosis of LCIS benefit from tamoxifen therapy?
Yes, 46% relative risk reduction in the NSABP-1 trial (hazard ratio 0.54).
53
Once a patient is diagnosed with LCIS, what is the recommended follow-up?
H&P every 6 to 12 months, along with annual diagnostic mammography.
54
Following recommended workup including H&P, diagnostic bilateral mammography, core needle biopsy
and pathology review, what further test is required in the workup of ductal carcinoma in situ (DCIS)?
Estrogen receptor (ER) and progesterone receptor (PR) determination
55
What are the two primary treatment options for women with DCIS?
1. Lumpectomy plus radiation.
2. Total mastectomy, with or without reconstruction
56
When is determination of lymph node status indicated in DCIS?
In pure DCIS, it is not indicated. However, if there is evidence of invasive disease at the time of the definitive
surgical procedure, lymph node status should be determined.
57
In patients diagnosed with DCIS with widespread disease (ie, more than two quadrants), what is the treatment of choice?
Total mastectomy with sentinel lymph node biopsy (SLNB) in the event that there is invasive disease on final pathology.
58
In patients with more limited disease, what is the treatment of choice?
Breast-conserving therapy (lumpectomy plus radiation).
59
In DCIS, is there a survival benefit in patients undergoing mastectomy rather than lumpectomy with whole breast irradiation?
No.
60
What are absolute contraindications for breast-conserving therapy in DCIS?
1. Indications for mastectomy versus lumpectomy:
a. mammographically identified multicentric disease
b. diffuse suspicious calcifications in the setting of biopsy proven DCIS c. persistent positive margins after re-excision
2. Contraindications for radiation:
a. previous moderate to high dose radiation to the breast or chest wall b. pregnancy
61
In margin-negative excision of DCIS, does whole breast radiation decrease rate of in-breast disease recurrence?
yes
62
In margin-negative excision of DCIS, does whole breast radiation improve overall survival or metastasis-free survival?
no
63
What is considered an adequate margin following DCIS resection?
This is a controversial issue. A recent meta-analysis has shown a greater recurrence risk with a margin <2 mm. However, there is a consensus according to NCCN guidelines that 10 mm is considered adequate while 1 mm is considered inadequate.
64
Following breast-conserving therapy, is there a benefit of hormonal therapy in the treatment of DCIS?
Yes, in hormone-receptor-positive disease, use of tamoxifen has been shown to decrease the risk of recurrence in the
ipsilateral breast and the risk of developing cancer in the contralateral breast.
65
What is included in follow-up for DCIS treatment?
H&P every 6 to 12 months, along with annual diagnostic mammography. In women receiving breast-conserving therapy, the first follow-up mammogram should be performed 6 to 12 months after the completion of breast-conserving radiation therapy.
66
With recurrence of DCIS, what is the recommended treatment in women who previously received breast-conserving therapy?
Mastectomy Breast conservation therapy cannot be repeated because of history of prior radiation.
67
According to the 2010 American Joint Committee on Cancer breast cancer guidelines, how is breast cancer staged?
According to TNM staging:
68
What is the most important prognostic factor following a diagnosis of breast cancer?
Node status.
69
In women receiving appropriate therapy, what is the 5-year relative survival for Stage I disease, Stage II disease, Stage III disease, and Stage IV disease?
Stage I: 100% Stage II: 86% Stage III: 57% Stage IV: 20%
70
What percentage of invasive carcinomas are ductal in origin?
85 to 90 ductal and approximately 10 lobular.
71
What is the recommended workup following diagnosis of invasive breast cancer?
H&P, complete blood cell count, platelet count, liver function tests, bilateral diagnostic mammography, breast ultrasound (if necessary), tumor ER and PR determinations, human epidermal growth factor receptor-2 (HER2) tumor status determination, pathology review, and consider genetic counseling in appropriate patients
72
When should breast MRI be considered for staging purposes (not screening)?
For breast cancer patients whose breasts cannot be adequately imaged with mammography and ultrasound.
73
What additional staging workup is indicated in patients with laboratory abnormalities, or abdominal/chest symptoms?
Bone scan, abdominal and pelvic ultrasound (US) or computed tomography (CT) or MRI, and chest x-ray or CT.
74
What additional staging workup is indicated in patients with clinical T3N1M0 disease?
Bone scan, abdominal and pelvic US or CT or MRI, and chest XR or CT.
75
Is PET scan indicated in the workup of breast cancer?
No, due to high false-negative rate in detecting small lesions (<1 cm) and low sensitivity for detecting axillary node
metastasis.
76
What is the most common site of disseminated disease?
Bone.
77
What are the treatment options for Stage I and Stage II invasive breast cancers?
Mastectomy with or without reconstruction, with a sentinel node biopsy (axillary dissection if SLNB is positive) Breast-conserving therapy (lumpectomy, SLNB, axillary dissection if SLNB is positive, and whole breast radiation)
78
What is a radical mastectomy, a modified radical mastectomy, simple mastectomy, or a lumpectomy?
1. Radical mastectomy:
r Rarely performed, includes removal of all breast tissue, pectoralis fascia, pectoralis musculature (major and
minor), and regional lymph nodes
2. Modified radical mastectomy:
r Removal of all breast tissue, including the nipple–areolar complex, along with the removal of level I and II
axillary lymph nodes 3. Simple mastectomy:
r Removal of all breast tissue, including the nipple–areolar complex 4. Lumpectomy:
r Excision of the primary tumor with preservation of the breast
79
What are relative contraindications for breast-conserving therapy?
1. Active connective tissue disease involving the skin.
2. Tumors greater than 5 cm.
3. Focally positive margins.
4. Positive margins after re-excision, or re-excision leaving a large defect with inadequate tissue for acceptable cosmetic preservation.
79
What are absolute contraindications for breast-conserving therapy in invasive breast cancer?
1. Previous moderate- to high-dose radiation to the breast or chest wall.
2. Pregnancy if the patient will require radiation therapy during the time of pregnancy.
3. Diffuse suspicious or malignant-appearing microcalcifications on mammography.
4. Widespread disease.
80
Following total mastectomy, what are indications for chest wall and regional radiation therapy?
1. Tumor >5 cm, regardless of axillary status.
2. Presence of four or more positive axillary lymph nodes.
3. Currently there is controversy over radiation therapy in cases of 1 to 3 positive axillary lymph nodes.
81
What is the positive predictive value of successful sentinel lymph node biopsy?
100%.
82
What is the negative predictive value of successful sentinel lymph node biopsy?
95%.
83
If sentinel node biopsy is positive, formal axillary dissection should involve what lymph node levels?
Levels I and II.
84
A minimum of how many lymph nodes should be provided to accurately stage the axilla?
10.
85
What patients are candidates for systemic adjuvant chemotherapy?
Tumor >1 cm, or those with positive lymph nodes.
86
If adjuvant chemotherapy is indicated, when should radiation begin?
Upon completion of chemotherapy.
87
Is there a difference in survival between patients undergoing a classic total mastectomy versus skin-sparing mastectomy?
No.
88
When should preoperative chemotherapy be considered and what is its rationale?
1. Stage IIA, Stage IIB, and T3N1M0 tumors.
2. Women who meet all criteria for breast conservation therapy with the exception of tumor size
Rationale: allows for downstaging of primary tumor, making breast conservation therapy possible in cases where mastectomy would otherwise be required.
89
In women with positive axillary lymph nodes, does chest wall and regional lymph node radiation improve disease-free and overall survival?
Yes.
90
What is HER2 and why is it important?
HER2, or HER2/neu is a member of the epidermal growth factor receptor family. HER2 is an acronym for human epidermal growth factor receptor 2. It is helpful for prognostic purposes and provides predictive information used in selecting optimal adjuvant/neoadjuvant therapy. Tumors with amplification of the HER2 gene have an increased risk of recurrence and generally carry a worse prognosis.
91
What is DNA microarray (ie, MammaPrint and Oncotype) technology and what is its importance?
1. Assay that determines the gene expression profile in breast tumor tissue.
2. Provides prognostic information and risk of distant metastases, particularly in node-negative disease.
3. Can help to identify patients who will benefit from hormonal therapy and/or chemotherapy in combination with hormonal therapy.
92
What is the goal of hormonal therapy?
To prevent tumor cell stimulation from estrogen.
93
What methods of hormonal manipulation are available?
1. Estrogen receptor blockers (tamoxifen).
2. Blockers of estrogen synthesis (aromatase inhibitors).
3. Ovarian ablation (surgical or medical).
94
How does tamoxifen work?
Tamoxifen is a selective estrogen receptor modulator. Tamoxifen acts as a competitive estrogen antagonist in breast tissue but not in other estrogen-sensitive tissues.
95
What patients are not candidates for hormonal therapy?
Patients with hormone receptor-negative breast cancer.
96
In premenopausal women with node-positive and hormone-receptor-positive disease, what adjuvant treatment is indicated?
Chemotherapy and hormonal therapy (tamoxifen should be delayed until completion of chemotherapy).
97
True/False. Patients with invasive breast cancer that are ER- or PR-positive should be considered for hormone therapy regardless of age, lymph node status, or adjuvant chemotherapy?
True
98
In women with ER-positive breast cancer, how greatly does adjuvant tamoxifen therapy decrease annual odds of recurrence and annual odds of death?
Decreases annual breast cancer recurrence rate (relative risk [RR]) by 39%. Decreases annual breast cancer death rate (RR) by 31%.
99
What is the optimal duration of adjuvant tamoxifen therapy?
5 years.
100
In postmenopausal women with early stage breast cancer, is there a benefit of adding an aromatase inhibitor for adjuvant treatment?
Yes, multiple studies have shown a survival benefit when adding aromatase inhibitors (AIs) to the adjuvant regimen in postmenopausal women. The ATAC trial showed AIs alone to be superior to treatment with tamoxifen or tamoxifen combined with an AI in postmenopausal women. Currently, first-line adjuvant hormonal therapy in postmenopausal women consists of AIs.
101
Which class of endocrine therapy drugs is associated with osteoporosis?
Aromatase inhibitors.
102
Which endocrine therapy drug is associated with increased risk of uterine cancer and DVT?
Tamoxifen.
103
What patients are candidates for systemic adjuvant chemotherapy?
Tumor >1 cm, or those with positive lymph nodes
104
What are some currently used chemotherapy regimens?
Preferred:
r docetaxel, doxorubicin, and cyclophosphamide
r doxorubicin, cyclophosphamide, and ± paclitaxel Other:
a. fluorouracil, doxorubicin, and cyclophosphamide. b. fluorouracil, epirubicin, and cyclophosphamide
105
In cases of operable breast cancer with indications for adjuvant chemotherapy, how greatly does chemotherapy decrease annual odds of recurrence and annual odds of death?
Age <50 years:
r reduces odds of recurrence (RR) by 35% r reduces odds of death (RR) by 27%
Age 50 to 69 years:
r reduces odds of recurrence (RR) by 20% r reduces odds of death (RR) by 11%
106
What is Herceptin?
Herceptin (trastuzumab) is a monoclonal antibody that targets the extracellular domain of HER2. Five trials using
adjuvant Herceptin have shown improved disease-free survival in patients with HER2-positive breast cancer.
107
What percentage of all breast cancers does male breast cancer account for?
0.8.
108
What percentage of male cancers does male breast cancer account for?
<1.
109
What acquired risk factors are associated with male breast cancer?
Age, hormonal imbalance (secondary to testicular disease), infertility, obesity, liver disease, and radiation exposure.
110
What genetic risk factors predispose to male breast cancer?
Klinefelter syndrome, family history, Jewish ancestry, and BRCA-2 mutation.
111
What is the lifetime risk of a male with a BRCA-2 mutation developing breast cancer?
Approximately 5% to 10%.
112
Is gynecomastia a risk factor for the development of male breast cancer?
No.
113
What is angiosarcoma?
A highly aggressive sarcoma originating from lymphatic or capillary endothelium. Angiosarcoma of the breast or upper extremity can occur as a primary tumor, or more commonly as a secondary tumor following treatment for breast cancer.
114
What is the time interval between breast cancer diagnosis and development of subsequent upper extremity or chest angiosarcoma?
5 to 10 years.
115
What syndrome describes upper extremity sarcoma development associated with lymphedema following radical mastectomy?
Stewart–Treves syndrome.
116
What is a risk factor for the development of angiosarcoma following breast cancer treatment?
Upper extremity lymphedema.
117
Where does angiosarcoma most commonly spread?
Hematogenous spread to the lungs and bones.
118
What is prognosis of angiosarcoma dependent on?
Histologic grade and tumor size.
119
What is Paget disease of the breast?
A rare manifestation of breast cancer characterized by neoplastic cells in the epidermis of the nipple–areolar complex.
120
How often is Paget disease associated with cancer elsewhere in the breast?
80% to 90%. The cancer may be invasive or DCIS.
121
What is the appropriate workup for a woman presenting with bleeding, ulceration, and/or pruritus of the nipple?
1. H&P
2. Diagnostic mammography.
3. Biopsy of any breast lesion.
4. Full-thickness skin biopsy of clinically involved nipple–areolar complex.
5. Breast MRI to identify extent of disease if skin biopsy is positive for Paget disease.
122
What are the appropriate treatment options for Paget disease of the breast?
1. Total mastectomy with or without reconstruction, with axillary staging.
2. Breast conservation therapy along with resection of the nipple–areolar complex, axillary staging, and whole breast radiation.
3. Adjuvant systemic therapy should be administered according to the stage of the cancer.
123
What is inflammatory breast cancer?
A rare, aggressive form of breast cancer estimated to account for 1% to 6% of breast cancer cases in the United States.
124
What clinical findings are required for a diagnosis of inflammatory breast cancer?
Requires erythema and dermal edema (peau d’orange) of one-third or more of the skin of the breast with a palpable
border to the erythema.
125
What is peau d’orange?
A swollen and pitted appearance to the skin (similar to that of an orange peel) secondary to stromal infiltration, lymphatic obstruction caused by tumor emboli within dermal lymphatics, and subsequent tightening of Cooper ligaments.
126
How is the diagnosis of inflammatory breast cancer made?
Clinically.
127
What is the recommended treatment of inflammatory breast cancer?
Multimodality treatment including preoperative chemotherapy, mastectomy with axillary lymph node dissection,
and radiation therapy.
128
With multimodality treatment, what is the relapse-free survival rate at 5 years?
50%.
