Breast Cancer Flashcards
1
Q
What is the most common cancer among women?
A
Breast cancer
2
Q
Has Mortality increased, stayed the same or decreased in patients with breast cancer since 1990?
A
Decreased
3
Q
In which parts of the world are incidence rates of breast cancer more elevated?
A
In economically developed regions - such as North America, western Europe, and Australia and New Zealand
4
Q
In which parts of the world are incidence rates of breast cancer are lower?
A
In economically developing areas such as sub-Saharan Africa and parts of Asia.
5
Q
Why is breast cancer incidence different in different parts of the world?
A
These differences across countries are likely related to:
- Breast cancer screening
- Reproductive factors
- Changes in fat intake and body weight, 4. Differences in age at menarche and/or lactation.
6
Q
What are the main reasons for the increase in incidence in breast cancer?
A
- Late childbearing age
- Increase in obesity
7
Q
What is the most common cause of cancer death worldwide in females?
A
Breast cancer
8
Q
What is the most common malignancy in the US?
A
Breast Cancer
9
Q
What is the most common cause of cancer-related death among women in the US?
A
Lung Cancer
10
Q
What is the second most common cause of cancer-related death among women in the US?
A
Breast Cancer
11
Q
In what race has breast cancer been historically more incident?
A
White women
12
Q
What are some factors that contribute to the racial difference in incidence in breast cancer?
A
- More frequent use of postmenopausal hormone replacement therapy in white women
- Higher screening mammography among white women
13
Q
What are the main difference in breast cancer mortality between black and white women? What are some factors that contribute to this difference?
A
The breast cancer mortality is approximately 40% higher among black women compared to white women.
- Breast cancer is more likely to develop before age 40 in black women than in white women
- Black women are also more likely to be dx at a more advanced stage
- Black women tend to have more high grade, triple negative tumors
Other factors…
14
Q
In what races have lower cancer releated incidence and mortality rates?
A
Asian, native America and hispanic women
15
Q
What are the main non-modiafiable risk factors for breast cancer?
A
- Age - older age >50
- Sex- Female
- Age at first birth >30 or nulliparity
- Age at menarche <12
- Age of menipause >50
- Hx of Atypical ductal hyperplasia or lobular carcinoma in situ
- First degree relatives
- Ashkenazi Jewish ethnicity
- Therapeutic irradiation to the chest <30 yrs
16
Q
What are the risk factors for breast cancer in males?
A
- Age >60
- Genetic predisposicion with BRCA2 or PALB2 mutations
- Klinefelter syndrome
- Testicular alterations that result in testosterone deficiency
- Syndromes that increase the estrogen to testosterone ratio (Obesity or Cirrhosis)
17
Q
What are the main familial risk factors for development of breast cancer?
A
Hx of breast and/or ovarian cancer in a family member dx before age 50
18
Q
What % of breast cancers are associated with BRCA1 or BRCA2?
A
5-10%
19
Q
Having a first degree relative with breast cancer increases risk of breast cancer by how many folds?
A
2X
20
Q
Having a first degree relative with breast cancer at an age <50 increases risk of breast cancer by how many folds?
A
3-4x
21
Q
Having 2 first degree relative with breast cancer increases risk of breast cancer by how many folds?
A
3-4x
22
Q
True or False: Having breast cancer in one breast increases the risk of developing contralateral disease?
A
True
23
Q
What are considered to be high penetrance mutations in breast cancer?
A
- BRCA1 and BRCA2
- TP53 (Li-Fraumeni syndrome)
- PTEN (cowden syndrome/harmatoma tumor syndrome)
- STK11 (Peutz-Jeghers syndrome)
- CDH1 (hereditary diffuse gastric cancer)
- PALB2
24
Q
What mutations are considered to be moderate penetrance in breast cancer?
A
- ATM
- CHEK1 truncating
- CHEK2 missense
- NF1
Others: BRIP1, MSH2, MLH1, MSH6, PMS2, EPCAM, NBN, RAD51C, RAD51D (insufficient evidence)
25
Who is the optimal family member to have genetic testing?
The youngest woman who carries either the dx of ovarian or breast cancer.
26
What is the main limitation of NGS testing in breast cancer?
We have limited understanding of risk associated with moderately penetrant genes and high likelihood of detecting variants of unknown significance.
27
What are the most common mutations in breast cancer?
Mutations localized in the BRCA1 and BRCA2 genes
28
True or False: BRCA1 and BRCA2 mutations are autosomal recessive.
False. They are autosomal dominant.
29
What is the function of the BRCA1 and BRCA2 proteins?
They function as tumor suppressors that protect chromosomal stability by enabling homologous recombination after dsDNA breaks.
30
What other proteins does BRCA2 protein associate with that are also important in breast cancer development?
1. RAD51
2. BRCA1
3. PALB2
31
What is the function of RAD51 protein?
Enzyme essential for homologous recombination
32
What is the interaction between PALB2 and BRCA2?
BRCA2 works in concert with PALB2 to facilitate recruitment with RAD51 and BRCA1 recruitment to sites of DNA damage resulting in repair.
33
What is the risk of breast cancer in patients with BRCA1 mutations?
55-70%
34
What is the risk of breast cancer in patients with BRCA2 mutations?
45-70%
35
True or False: BRCA1 mutations confer higher risk for ovarian cancer than BRCA2 mutations.
TRUE: BRCA1- 40-45% vs BRCA2 15-20%
36
What is the risk of male breast cancer in patients with BRCA2 mutations?
7%
37
What are considered the 3 founder mutations in the BRCA1 and 2 genes?
1. 185delAG in BRCA1
2. 5382insC in BRCA1
3. 6174delT in BRCA2
38
True or false: BRCA2 mutation carriers are more likely to develop triple negative breast cancer than are BRCA1 mutation carriers or non-BRCA mutation carries?
FALSE.
BRCA1 mutation carriers are more likely to develop triple negative breast cancer than are BRCA2 mutation carriers or non-BRCA mutation carries
39
Is Li-Fraumeni syndrome associated with higher risk of breast cancer?
Yes.
90% lifetime risk of a malignancy developing, which includes breast cancer in women younger than 30 years, in addition to other types of malignancies
40
True or false: HER2-positive breast cancer is more prevalent in women with TP53 germline mutation compared with women without the TP53 mutation
TRUE
41
What gene is associated with Cowden syndrome?
PTEN
42
What types of cancers are seen in patients with Cowden syndrome?
1. Breast cancer
2. Thyroid cancer
3. Endometrial cancer
4. Colon cancer
5. Renal cancer
43
What specific physical findings can be seen in patients with Cowden syndrome?
Macrocephaly, hamartomas, autism, and trichilemmomas of the face, hands, and feet.
44
What type of breast cancer is associated to germline pathogenic variants in cadherin 1 gene?
Invassive lobular carcinoma
45
Do premenopausal levels of estrogen affect the risk of breast cancer in postmenopausal state?
Yes.
Increased levels of premenopausal endogenous hormones are associated with an increased risk of disease among postmenopausal women.
46
Does lactation convey protection against breast cancer?
It may however, the duration of lactation required for this benefit is not well defined.
47
Does using hormonal contraceptives increase the risk of breast cancer?
Yes.
The use of contemporary hormonal contraceptives has been associated with a higher risk of breast cancer compared with women who had never used hormonal contraceptives; however, the absolute increase in risk is small.
48
What type of breast cancer is associated with early onset menarche, late age of menopause and nulliparity?
Elevated risk of hormone-receptor (HR)-positive disease.
49
Is triple negative breast cancer associated with nuliiparity or age at first full term pregnancy?
No.
TNBC is associated with an increasing number of births.
50
Does hormonal therapy increase the risk of breast cancer?
Yes.
51
True or false: The risk of breast cancer associated with hormonal therapy is temporary and returns to normal after 2 years of discontinuation of hormonal therapy.
True.
52
True or false: Women taking combination menopausal hormone therapy also have been found to have a more advanced stage of breast cancer at the time of diagnosis.
True
53
True or False: Survivors of Hodgkin lymphoma and other hematologic malignancies who received therapeutic mediastinal or mantle-field radiation have a higher risk of breast cancer.
TRUE
54
What is the median time to the development of breast cancer after having mediastinal radiation for another malignancy?
18 years
55
What are the screening recommendations for patients with a hx of thoracic radiation received between the ages of 10 and 30 years?
Annual screening mammograms and annual breast magnetic resonance imaging (MRI) start at the age of 25 years.
56
How is Mammographic density is classified?
According to the proportion of radiopaque areas on a mammogram, representing epithelial and stromal tissue, relative to radiolucent areas, representing fat
57
What are the 4 categories of breast density composition according to the ACR?
A. The breasts are almost entirely fatty.
B. The breasts have scattered areas of fibroglandular density.
C. The breasts are heterogeneously dense, which may obscure small masses.
D. The breasts are extremely dense, which lowers the sensitivity of mammography.
58
According to the ACR what categories of breast density are considered "dense"?
Categories C and D.
## Footnote
C. The breasts are heterogeneously dense, which may obscure small masses.
D. The breasts are extremely dense, which lowers the sensitivity of mammography.
59
Do women with more dense breast tissue have a higher risk of developing breast cancer?
Yes.
Women with \> 75% breast density have a four- to six-fold higher risk of disease.
60
What exogenous factors can result in increased mammographic density?
Exogenous hormone use, such as menopausal hormone therapy or oral contraceptives can cause increased mammographic density.
61
What is the main issue associated with increased mammographic density?
Masking of cancer by superimposition of overlapping, radiopaque, dense breast tissue. Mammographic density is a principal factor in the failure of mammography to detect cancer.
62
What types of benign proliferative breast changes are associated with a higher risk of breast cancer? How high is this risk?
- Atypical ductal hyperplasia (ADH) -4x
- Atypical lobular hyperplasia (ALH) - 4x
- Lobular carcinoma in situ (LCIS) - 10x
63
What are the pathological features of atypical ductal hyperplasia?
- Loss of stroma between acini
- Cellular pleomorphism
- Cellular hyperchromasia
- "Cribiforming" - "Swiss cheese"
- Increased mitoses
- "Roman Bridges"
64
What types of benign proliferative breast lesions do not seem to increase breast cancer risk?
Benign proliferative lesions without atypia seem not to increase breast cancer risk.
65
What is the risk of breast cancer developping in patients with atypical hyperplasia over 25 years?
30%
66
What is the best next step after dx of ADH using core needle biopsy?
It is recommended that most individuals undergo an excisional procedure to exclude the possibility of an associated invasive carcinoma.
67
What is the next best step for ALH and LCIS reported using a core needle biopsy?
-Given the small reported risk of upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma, incidental radiologic-pathologic concordant cases diagnosed on core needle biopsy **no longer require surgical excision.**
68
What is ADH (breast mass)?
Atypical ductal hyperplasia:
* Benign proliferative breast disease with some but not all features of low grade DCIS
* Confined to the ducts
69
What genetic changes can be seen in ADH?
Loss of 16q and 17p
70
What are the 3 main structures found in the breast?
1. Lobe
2. Ducts
3. Fatty tissue
71
Consumption of one alcoholic beverage/day is associated with what % increase risk of breast cancer?
12%
72
What is the most common used risk assessment tool for breast cancer?
The Modified Gail Model
73
What does the modified Gail model measure?
- risk assessment tool for breast cancer
- incorporates nongenetic factors:
- Age
- Age at menarche and full term pregnancy or nulliparity
- number of breast biopsies and presence of atypical hyperplasia
- number of first degree relatives with breast cancer
- race
74
What are recommended methods for the prevention of cancer in patients with BRCA1 and BRCA2 mutations?
It is recommended that women with BRCA1 and BRCA2 mutations undergo Risk Reducing bilateral salpingo-ooforectomy typically between ages 35 and 40 years and on completion of childbearing
75
True or False: Bilateral Salpingo-Oophorectomy in patients with BRCA1 mutations can be delayed until ages 40-45 yrs?
FALSE.
NCCN guidelines specifically note it is reasonable to delay RRSO until ages 40 to 45 years in patients with a BRCA2 mutation, because the median age of onset of ovarian cancer tends to occur 8 to 10 years later than in patients with a BRCA1 mutation.
76
TRUE or FALSE:
RRSO decreases the risk of ovarian cancer by approximately 50%.
FALSE.
## Footnote
A decrease in the risk of ovarian cancer (which includes primary peritoneal and fallopian tube cancers) by approximately 85% (hazard ratio, 0.14)
77
TRUE or FALSE:
Bilateral RRM reduces the risk of breast cancer by \> 90% in women with hereditary breast and ovarian cancer syndromes.
TRUE
78
Should prophylactic bilateral risk-reduction mastectomy be offered in patients with BRCA mutations?
Yes.
79
Does reconstructive surgery after mastectomies increase the risk of breast cancer in patients with BRCA mutations?
No. Reconstructive surgery after mastectomies does not appear to increase breast cancer risk.
80
81
TRUE OR FALSE: Several studies have shown that tamoxifen reduces the incidence of invasive breast cancer by 30%
TRUE
82
TRUE OR FALSE: Tamoxifen improves survival in patients with invassive breast cancer?
FALSE
83
Name 4 possible side effects of tamoxifen
1. Increases the risk of endometrial cancer
2. Increases the risk of VTE
3. Increased risk of cataracts
4. Hot Flashes
5. Bone loss in premenopausal women
84
Name a second generation SERM
Raloxifene
85
What side effect is not seen with raloxifene that is seen with tamoxifen?
Raloxifene does not increase the risk of endometrial cancer
86
What study compared Raloxifene and Tamoxifene?
The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-2 Study of Tamoxifen and Raloxifene (STAR) trial
87
According to the NSABP and STAR trial which is more efficacious in reducing the risk of invasive breast cancer?
Tamoxifen is more effective, but Raloxifene has less side effects.
88
What is the mechanism of action of SERMs (tamoxifen, raloxifene)?
Competitive inhibitors of estrogen binding to estrogen receptors
- mixed antagonistic and agonist activity depending on target tissue:
- Provide protection against manopausal bone loss
- Lower total and LDL cholesterol
- Tamoxifen induces endometrial hyperplasia
89
Which 3 major classes of endocrine therapies are available for treatment and/or prevention of ER-positive breast cancers?
1. SERMs - Selective estrogen receptor modulators (tamoxifen, raloxifene)
2. SERDs - Selective estrogen receptor downregulators (fulvestrant)
3. AIs - Aromatase inhibitors
90
What is the mechanism of action of fulvestrant (SERD)?
Competitive antagonist of estrogen binding - causes degradation of the ER protein.
91
What is meant by "tamoxifen resistance" in patients with breast cancer?
Resistance to tamoxifen may occur in patients taking drugs that alter the CYP2D6 metabolism of the agen including:
-SSRIs
Some patients have intrinsic mutations in the ER that are resistant to tamoxifen
92
Name 3 aromatase inhibitors used for management of breast cancer
1. Anastrozole
2. Letrozole
3. Exemestane
93
For which patients with breast cancer are aromatase inhibitors preferred as opposed to SERMS?
For posmenopausal patients with breast cancer.
94
What is the mechanism of action of aromatase inhibitors?
AIs suppress plasma estrogen levels by inhibiting or inactivating aromatase, the enzyme responsible for the peripheral conversion of androgens to estrogens.
95
Which patients benefit most from endocrine therapy for breast cancer risk reduction?
1. Patients with prior diagnosis of atypical hyperplasia or lobular carcinoma in situ
2. 5- yr risk by the NCI breast cancer risk assessment tool of at least 3%
3. 10 yr risk by the IBIS/Tyrer-Cuzick risk calculator \>5 %
4. RR\>2x than average for age gp if age 45-69yrs
5. RR\>4 x than the average gp if age 40-44 yrs
96
What are the recommendation for screening for breast cancer according to the USPSTF?
Initiating biennial screening at age 50 years and continuing until age 74 years.
97
Which patients should be screened annually for breast cancer using MRI?
1. BRCA1/2 mutation carriers
2. First-degree relative of a BRCA carrier, who is untested for the presence of a BRCA mutation
3. Lifetime risk ≥ 20%, as defined by BRCAPRO or other models that largely depend on family history
4. Radiation to chest between the ages 10 years and 30 years;
5. Li-Fraumeni syndrome and first-degree relatives
6. Cowden syndrome.
98
When do you start screening women who have received mantle chest-radiation treatment of lymphoma?
10 yrs after completion of radiation therapy
99
When do you start screening with MRI women at high risk because of familial (nonhereditary) reasons?
Initiation of screening should begin approximately 10 years earlier than the age of the youngest woman in the family diagnosed with breast cancer, but not later than age 40 years.
100
When do you use US to evaluate a palpable breast mass?
In patients younger than 30 yrs
101
What is the difference between diagnostic mammography and screening mammography?
Diagnostic mammography differs from screening mammography in that it adds images to the standard two-view imaging used with screening (ie, craniocaudal and mediolateral oblique)
102
What type of biopsy is preferred in patients with suspicious imaging findings or suspicious palpable breast mass?
Core needle biopsy
103
When should screening mammographies and annual MRI be started on patients with BRCA mutations?
For women with BRCA mutations who have not undergone risk-reducing surgery, annual MRI of the breasts is recommended beginning at age 25 years and annual mammography beginning at age 30 years.
104
What is the most important anatomic prognostic indicator for localized breast cancer?
Presence of tumor in the axillary lymph nodes (includes intramammary LN).
Regardless of other characteristics of the breast cancer, having more axillary lymph nodes involved with disease is related to increased risk of systemic recurrence and decreased disease-specific survival.
105
106
What is the difference between macrometastasis bs micrometastasis when if comes to LN involvement and breast cancer and which one is worse?
Lymph nodes with macrometastasis (\> 2 mm) or micrometastasis (\> 0.2 mm or \> 200 cells, but none \> 2 mm) are counted as nodal involvement.
There is a greater risk for disease recurrence and death with macrometastatic disease.
107
When determining T staging in breast cancer, what happens if there are more than 1 foci of involvement?
Tumor staging is based on the size of the largest tumor and does not take into account other smaller foci. The sizes of multiple tumors should not be added. The presence of multiple tumors is noted by adding the (m) modifier to T category
108
What is the most common hystological tumor type in breast cancer?
IDC (infiltrating ductal carcinoma)
109
What is particular about the metastatic pattern in infiltrating lobular carcinoma?
ILC tend to be ER positive and HER 2 negative.
In metastatic disease there tends to be involvement of serosas, ovary, meninges, and GI tract.
110
Which histological types of breast cancer are assocaited with favorable prognosis?
1. Tubular and mucinous types
111
Which histological subtypes of breat cancer are associated with an unfavorable prognosis?
Metaplastic carcinomas
112
What are the biologic prognostic indicators in breast cancer?
1. Tumor grade
2. Hormone receptors
3. HER2 expression
4. KI67
5. Intrinsic molecular type
6. Gene expression
113
What are the anatomic prognostic indicators in breast cancer?
1. LN invovlement
2. Lymphovascular invasion
3. Tumor size
4. Histology
114
How is tumor grade determined in breast cancer?
The histologic grading system for breast cancer is a semiquantitative evaluation of morphologic features consisting of the percentage of tubular formation, degree of nuclear pleomorphism, and mitotic count within a predefined area.
On the basis of the scoring of these characteristics, three grades reflect breast cancer differentiation: low, intermediate, and high. The histologic grade is an independent prognostic indicator that has been closely linked to molecular features of breast cancer.
115
What is the defnition of ER and PR positivity?
The 2010 ASCO/College of American Pathologists (CAP) guideline defines a tumor as ER or PR positive if 1% or more of tumor cell nuclei are immunoreactive.
116
What percentage of breast cancers are ER positive?
ER-α is expressed in approximately 70% of invasive breast cancers
117
Do ER positive PR negative breast cancer exist?
Yes. They are uncommon but they do exist
118
What are patient characteristics are associated with ER/PR positive breast cancer?
Older patient age, lower tumor grade and negative lymph nodes
119
What % of breat cancers are HR negative?
25%
120
What % of breast cancers are TNBC?
15%
121
Which bone mass preserving agents have been shown to decrease the change of bone metastases in women with breast cancer?
1. Zoledronate (more than denosumab)
2. Denosumab
122
What is the classification of phyllodes tumors?
1. Benign
2. Borderline
3. Malignant
123
What are Phyllodes tumors composed of?
They are composed of both stromal and epithial components.
124
What is the prognosis of a phyllodes tumor based on?
Surgical margins after resection.
Margins\>1cm
125
What is a common site of metastasis for Phyllodes tumors?
Lungs
126
What is the treatment of Phyllodes tumors?
Mainly resection.
Options for treatment of metastatic disease can be based on therapies for soft tissue sarcomas.
127
When is chemotherapy indicated for phyllodes tumors?
hemotherapy is not indicated unless the phyllodes tumor is malignant in nature and metastatic.
128
Is radiation suggested as adjuvant therapy for a benign phyllodes tumor?
No
129
Do Phyllodes tumors express estrogen/progesterone receptors?
Yes they can.
130
Can phyllodes tumors be treated with hormonal therapy?
No. It is their stromal component which is the principle neoplastic population responsible for metastatic behavior.
131
What is the treatment of a intraductal papilloma of the breast?
Excision.
132
What are some of the symptoms that can be associated with papilloma of the breast?
They may be asymptomatic, or present with a palpable mass, tenderness, and bloody discharge
133
TRUE OR FALSE. Papillomas of the breast are mostly seen in patients +50.
FALSE. Papillomas mostly occure in younger premenopausal patients with peak age 35-55
134
TRUE OR FALSE. Breast papillomas are all beningn lesions.
FALSE. The vast majority are benign; however, they commonly co-present with other premalignant features in the involved breast
135
What is the most appropriate management for breast papillomas?
Management is typically surgical resection with no need to perform other studies or stage, as they do not metastasize. Systemic therapies are not indicated solely for this entity. Complete resection with adequate analysis of the surrounding breast tissue is important to ensure that other entities increasing one's risk for breast cancer can also be identified and managed appropriately.
136
What is the definition of inflammatory breast cancer?
Clinical diagnosis in the setting of documented invasive breast ca and is characterized by a rapid onset of clinical changes including:
- skin erythema, warmth, edema
- Breast enlargement and pain
137
What is the mechanism of extension/clinical changes seen in inflammatory breast cancer?
The classic physical findings of the breast are due to damage of the dermal lymphatics caused by tumor emboli
138
What is the most common receptor pattern in inflammatory breast cancer?
Although all subtypes are seen in IBC, HER2-positive or triple-negative subtypes are common.
139
What is the treatment of inflammatory breast cancer?
IBC is treated with neoadjuvant chemotherapy (anthracycline- and taxane-based regimens) followed by mastectomy with levels I and II ALND and PMRT with comprehensive regional nodal irradiation (The chest wall and regional lymph nodes (supraclavicular, infraclavicular, internal mammary) are included in the treatment field.)
140
What is the treatment of HER2 positive inflammatory breast cancer?
HER2-positive IBC should be treated with a dual HER2-targeted neoadjuvant regimen with trastuzumab and pertuzumab.
141
TRUE OR FALSE: Breast conservation surgery is contraindicated in inflammatory breast cancer.
TRUE. As is SLN.
142
TRUE or FALSE: DFS is worse with IBC compared with noninflammatory breast cancer.
TRUE
143
What is the mechanism of action of trastuzumab emtansine?
It is an antibody drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1) - a maytansine drivative and microtubule inhibitor
144
What type of trial was the KATHERINE trial and what was it comparing?
- Phase 3 open label trial
- involving HER2+ early breast cancer patients who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing taxane (with or without anthracycline) and trastuzumab.
- 1486 patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles
145
What were the main results if the KATHERINE trial?
1. DFS at 3 yrs 88.3% in T-DM1 gp vs 77% in trastuzumab gp
2. Invassive DFS was significantly higher in TDM1 gp than in the trastuzumab gp (HR 0.50 CI 0.39-0.64)
3. More side effects were found in the T-DM1 gp vs trastuzumab gp
146
What side effects are most commonly expected with ado-trastuzumab emtansine?
Fatigue, nausea, thrombocytopenia, increased LFTs, neuropathy
147
What type of study was the IMpassion130 trial and what was it comparing?
1. Phase 3 trial, random assigned pateitns with untreated metastatic TNBC to receive atezo + nab paclitaxel vs placebo + nab paclitaxel
2. Primary end points were PFS and OS
148
What were the main results if the IMpassion130 trial?
1. ITT analysis median PFS was 7.2 mo with atezo + nab-paclitaxel vs 5.5 mo with nab paclitaxel alone - HR death or progression 0.8 CI 0.69-0.92. mOS - 21.3 mo vs 17.6 mo HR 0.84 CI 0.69-1.02
2. Among patients with PDL1 positive tumors (\>1%) the median PFS was 7.5 vs 5 mo HR 0.62 CI 0.49-0.78 . mOS 25 mo vs 15.5 mo HR 0.62 CI 0.45-0.86
149
Are there randomized controlled studies done to determine if yoga improves cancer related fatigue?
YES!
150
Is breast cancer associated with breast pain in patients with no other clinical signs of cancer (ex: mass, erythema, edema)?
NO pain is not associated with breast cancer if there are no other clinical symptoms.
151
What is the most common histologic type of breast cancer?
Invasive ductal carcinoma
152
What is the second most common histological type of breast cancer?
Invasive lobular carcinoma
153
What specific histological marker is NOT present in lobular carcinoma to differentiate it from other breast cancer types?
E-cadherin
154
What is the definition of carcinoma in situ?
Proliferation of malignant apearing mammary epoithelial cells that remain confined within the basement membrane without evidence of invasion in the stroma.
155
What are the different levels of histological grading in breast cancer?
Grading is a microscopic feature which describes the grade of differentiation of a tumor.
It is based on: nuclear and architectural characteristics.
Grade 1: well diferentiated
Grade 2: moderately differentiated
Grade 3: Poorly differentiated
Histologic grading has prognostic significance
156
What is the molecular classification of breast cancer?
4 groups:
1. Luminal A
2. Luminal B
3. HER-2 enriched
4. Basal like
157
Which is the most common molecular subtype of breast cancer?
Luminal A
158
Do luminal A breast cancers have a good prognosis?
Yes
159
What is the most commonly seen metastasis for luminal A cancers?
Bone mets
160
Which molecular type of breast cancer is mostly associated with visceral metastases?
Luminal B
161
What are the indications for use of Fam-transtuzumab deruxtecan nxki?
Treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received 2 or more prior anti-HER2 based regimens in the metastatic setting
162
What is the mechanism of action of Fam-transtuzumab deruxtecan nxki?
Antibody-drug conjugate composed of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor
163
What is the preferred adjuvant endocrine therapy in premenopausal patients with early breast cancer with high risk of recurrence?
Maintenance therapy with ovarian suppresion + endocrine therapy (AI or tamoxifen)
164
What is the most likely dx in a pt that received prior radiation therapy for breast cancer that now presents with asymptomatic skin changes?
Radiation induced changes or radiation induced angiosarcoma.\
Angiosarcomas may manifest as cutaneous or subcutaneous, flat or nodular, or localized or multifocal lesions and can have an appearance similar to that of benign angiomas or atypical telangiectasia.
165
What is the treatment for radiation induced angiosarcoma?
Aggressive surgery is the standard of care and usually involves mastectomy to obtain wide margins. Recurrence rates are high and these tumors will often spread to the liver and lung.
166
Is there a role for trastuzumab in HER 2 + DCIS?
No.
167
What medication can you give to patients with advanced unresectable or metastatic HER2 positive breast cancer who have brain mets?
Tucatinib
168
What type of chemoprevention is indicated for premenopausal women with breast biopsy demonstrating atypical ductal or lobular hyperplasia or lobular carcinoma in situ?
Tamoxifen 20 mg daily for 5 years.
169
What are the main prognostic factors for recurrence of breast cancer?
Clinicopathologic features such as:
1. Tumor size and grade
2. Number of axillary lymph nodes with metastasis.
170
What is the preferred adjuvant endocrine therapy of choice in male breast cancer?
Tamoxifen
171
What is the first line treatment for metastatic HER 2 positive breast cancer?
Six cycles of docetaxel, trastuzumab, and pertuzumab (THP)
172
When is olaparib indicated in patients with breast cancer?
Olaparib is only indicated for patients with germline BRCA1 or BRCA2 mutations.
173
What patients can benefit from sacituzumab govitecan treatment?
Based on the ASCENT trial sacituzumab govitecan can benefit patients with relapsed refractory metastatic triple-negative breast cancer (without brain mets).
ASCENT trial - sacituzumab govitecan vs dealer's choice chemo in 468 pts.
PFS 5.6 mo vs 1.7 mo (HR0.41 P\<0.0001)
174
What is the mechanism of action of Sacituzumab govitecan?
Antibody–drug conjugate composed of an antitrophoblast cell-surface antigen 2 (Trop-2) IgG1 kappa antibody coupled to SN-38, the active metabolite of irinotecan and a topoisomerase I inhibitor
175
What are the risk factors associated with locoregional recurrence after breast conserving therapy?
1. Young age \<35
2. BRCA1 and BRCA2 mutations
3. Margin of resection - positive margins
4. Type of breast cancer - triple negative
5. No irradiation
6. No systemic adjuvant treatment
176
What are absolute contraindications to undergo radiation therapy for breast cancer?
1. Ongoing pregnancy
2. Diffuse suspivious microcalcifications
177
What are relative contraindications to undergo radiation therapy for breast cancer?
1. Active connective tissue disease involving skin (scleroderma or lupus)
2. Tumor \>5cm
3. Focally positive margin
178
Describe the lymphatic drainage of the breast
Breast lymphatic drainage occurs through a superficial and deep lymphatic plexus and \>95% of drainage is through axillary LN and 5% via internal mammary LN.
Axillary LN are divided into levels based on their relationship to pectoralis minor muscle:
Level 1: lateral to lateral border of pectoralis minor muscle
Level 2: behing pectoralis muscle
Level 3: medial to the medial border of pectoralis minor muscle
179
180
What is the age range for breast cancer screening in patients with an average risk for breast cancer according to the USPSTF?
50-74 yrs
181
What is the optimal method for screening patients with a high risk of breast cancer?
Breast MRI
182
What are the 6 situations in which annual breast MRI screening is used as an adjunct to a mammography?
1. BRCA1/2 mutation carriers
2. first degree relative of BRCA carrier who is untested
3. lifetime risk \>20% as defined by BRCAPRO or other models based on family hx
4. Radiation to the chest between ages 10-30 yrs
5. Li-Fraumeni syndrome and first-degree relatives
6. Cowden syndrome
183
At what age can you start screening patients with hereditary breast cancer syndromes?
- Age 25 with annual breast MRI and biannual clinical breast exam
184
When do you start screening patients that have received chest radiation?
-10 yrs after completing radiation therapy
185
At what age do you start breast cancer screening for patients that have a high risk of breast cancer for familial (non-hereditary) reasons?
-Start screening approximately 10 yrs earlier than the age of the youngest woman in the family diagnosed with breast cancer but not later than 40 yrs
186
What is the first diagnostic procedure performed to evaluate a palpable breast mass in a woman \<30 yrs?
US
187
188
What is the first diagnostic procedure performed to evaluate a palpable breast mass in a woman \>30 yrs?
Diagnostic mammography
189
What are the differences between diagnostic mammography and screening mammography?
Diagnostic mammography differs from screening mammography in that it adds images to the standard two-view imaging used with screening (ie, craniocaudal and mediolateral oblique).
190
What % reduction in breast cancer mortality is obtained by performing screening mammography?
14-32% reduction in breast cancer-related mortality in patients ages 50-70 yrs. Data on 40-49 ys and 70+ yrs are less robust.
191
What are the screening recommendations for patients with BRCA mutations?
Women with BRCA mutations who have not undergone risk-reducing surgery, annual MRI of the breasts is recommended beginning at age 25 years and annual mammography beginning at age 30 years.
192
In breast cancer what is included in an anatomic stage?
The anatomic stage is solely based on TNM staging.
193
In breast cancer what is information is included in the clinical prognostic staging?
1. TNM
2. Markers including tumor grade
3. Biomaker staging - HER2, ER, PR
194
195
What is the most widely used multigene panel in breast cancer?
Oncotype Dx score
196
TRUE or FALSE: LCIS is considered a benign entity.
TRUE
197
What is the most important anatomic prognostic indicator for localized breast cancer?
Axillary LN involvement
198
Explain the different types of LN involvement and how it affects prognosis
The size of the metastatic component within the axillary LN is important for prognosis.
LN with macrometastasis (\>2mm) or micrometastasis (\>0.2mm or \>200 cells but none \>2mm) are counted as nodal involvement.
There is a greater risk of disease recurrence and death with micrometastatic disease as compared to micrometastatic disease
199
In terms of prognosis, what is larger tumor size associated with?
-increases the risk of ipsilateral recurrence after breast conservation surgery
200
What type of receptor is HER2?
Epidermal growth factor receptor tyrosine kinase family
201
In what % of breast cancer is HER2 overexpression detected?
Approximately 20% of all breast cancers.
202
What is MammaPrint?
MammaPrint is a 70 gene signature that classifies tumors into either high or low-risk recurrence.
203
What is Oncotype Dx?
It is a 21 gene expression assay, the most widely used prognostic test.
-used to assess the risk of systemic recurrence among women with ER + breast cancer treated with tamoxifen for 5 yrs
RS \<18 Low
RS 18-30 intermediate
RS\>30 high
204
In which types of breast cancer patients have the 21 and 70 gene panels been validated?
- HR +
- HER2 -
- Node negative breast cancer
