Early stage Breast Cancer Part 1 Flashcards
The _______ of the breast extends into the region of the low axilla and is frequently referred to as the axillary tail of Spence. This anatomical feature results in the _________ of the breast containing a greater percentage of total breast tissue compared with the other quadrants, and, therefore, a greater percentage of breast cancers occur in this anatomical location
upper-outer quadrant (38.5%)
The surface of the breast has deep attachments of fibrous septa, called _______, which run between the superficial fascia (attached to the skin) and the deep fascia (covering the pectoralis major and other muscles of the chest wall). Skin dimpling may be caused by tumors affecting these supporting structures.
Cooper’s ligament
The function of the ____ is to produce milk
The function of the _____ is to transport lactation products to the nipple
lobules
Ducts
Most breast cancers develop at the interface between the ductal system and the lobules, a region called the ______.
terminal ductal lobular unit
The predominant lymphatic drainage of the breast is to axillary lymph nodes, which is commonly described in three levels, based on the relation of the lymph node regions to the _______.
pectoralis minor muscle
Describe the axillary lymph node levels with respect to pectoralis minor muscle
The level I axilla is caudal and lateral to the muscle,
level II is beneath the muscle, and
level III (also known as the infraclavicular region) is cranial and medial to the muscle.
A standard axillary lymph node dissection resects the tissue and lymph nodes within what axillary levels?
levels I and II
Located in parasternal space
Anatomical region: internal mammary vessels
Usually lie 3 to 4 cm lateral to midline
Majority of involvement is limited to lymph nodes in the first three interspaces
Breast CA that develop in the medial, central, or lower breast more commonly drain to the IMC
Internal mammary nodes
Axillary drainage is more common than internal mammary drainage, even in inner quadrant lesions
However, internal mammary drainage was present in over __% of lower inner quadrant lesions.
50%
most frequently diagnosed cancer in women
2nd among cancer deaths in women (after lung cancer)
incidence is lower in African American women
age of onset is younger and African American women are more likely to be diagnosed at a more advanced stage
Breast cancer
The risk of breast cancer decreases exponentially up to the age of menopause, at which time the rate of increase in the risk slows significantly
True or false?
False
The risk of breast cancer increases exponentially up to the age of menopause, at which time the rate of increase in the risk slows significantly
Worldwide case control study, MacMahon et al:
Demonstrated a nearly linear relation between relative risk of breast cancer and age at first birth, with women aged 20 to 25 having nearly a _______ in the relative risk of breast cancer compared with nulliparous women. Interestingly, for women whose first childbirth occurred over age 35, the risk appears greater than nulliparous women. Data on the effect of breastfeeding are not as strong as the data on age at first childbirth, but they do suggest a protective effect.
50% reduction
The Oxford Collaborative Group:
Analysis of 47 studies evaluating breastfeeding and breast cancer risk and reported a decrease in relative risk of breast cancer by ____ for each 12 months of breastfeeding
4.3%
early menarche and late menopause contributing significantly to breast cancer risk
T or F?
True
Randomized trial of postmenopausal hormone therapy from the Women’s Health Initiative Study:
compared estrogen and progestin with placebo was closed prematurely, demonstrating a ____% increase in breast cancer, coronary heart disease, stroke, and pulmonary emboli.
24%
National Comprehensive Cancer Network (NCCN) published guidelines for genetic testing. In the context of pre- and posttest counseling, the NCCN recommends that genetic testing be offered when?
National Comprehensive Cancer Network (NCCN) published guidelines for genetic testing. In the context of pre- and posttest counseling, the NCCN recommends that genetic testing be offered when:
1. The individual has a family history of a known BRCA1/BRCA2 mutation, 2. Personal history of breast cancer plus one of the following: a. Diagnosed age 45 years or younger b. Diagnosed age ≤50 years with one or more close blood relatives with breast cancer ≤50 years c. Two breast primaries when first breast primary occurred before age 50 d. Diagnosed at any age, with two or more close blood relatives with breast and/or epithelial ovarian/fallopian tube/primary peritoneal cancer at any age e. Close male relative with breast cancer f. An individual of ethnicity associated with higher mutation frequency (e.g., Ashkenazi Jewish). 3. Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer, or 4. Personal history of male breast cancer.
Land et al. reviewed reports on three populations of patients exposed to ionizing radiation by atomic bombings, multiple fluoroscopic examinations for tuberculosis, and multiple examinations for mastitis. They concluded that the risk of radiation-induced cancer of the breast increased approximately linearly with increasing dose and was heavily dependent on age at exposure.
True or False?
True
Alcohol Consumption
In an analysis by the Oxford Group of 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without breast cancer, women with daily consumption of _____ drinks a day had a 50% higher breast cancer risk
Mammographic Density
four or more
Mammographic Density
Boyd et al. and Byrne et al. noted that women with 75% or greater breast density parenchymal patterns on the mammogram had a ____fold greater risk of breast cancer
Five
Approximately ___% of breast CA pxs have familial breast cancer
10%
increased risk for a variety of cancers, including childhood sarcomas, gynecologic tumors, and breast cancer. Breast cancer is the most common malignancy in patients with Li-Fraumeni syndrome; the lifetime risk is estimated to be 90%.
Mutations in p53
“guardian of the genome”
p53
Li-Fraumeni syndrome
Lifetime risk of breast CA: estimated to be ____%
90%
Lifetime risk
Breast cancer of 65-85%
Ovarian cancer up to 50%
May develop more frequently: colon and prostate CA
BRCA1
Lifetime risk
Breast cancer: mirrors that of BRCA1
Ovarian cancer: much less than that of BRCA1
Associated with male breast CA and pancreatic CA
BRCA2
Study to test efficacy of 5yrs of tamoxifen in the prevention of breast CA
Results:
tamoxifen reduced the rates
Invasive breast CA – 49%
Noninvasive breast CA - 50%
86% risk reduction - with a history of atypical ductal hyperplasia
56% risk reduction – with a history of LCIS
NSABP P-1 trial
most breast cancer is a consequence of a series of _____ mutations
somatic
Using estimates of tumor doubling time, average of approximately __ years for a tumor to reach palpable size
5
Involvement of the superficial and deep lymphatics
Edema of the skin (peau d’orange)
Caused by involvement of Cooper’s ligament
Skin dimpling
common route of spread of breast carcinoma
10-40% of newly diagnosed T1 and T2 breast CA have pathologic evidence of _______
axillary nodal metastases/spread
In Voogd et al, lymph node metastases were associated with:
lymph node metastases were associated with:
tumors larger than 1 cm (P = .001)
moderate or poorly differentiated nuclear grade (P = .005)
high fraction of cells in the growth phase (S phase) of the cell cycle (P = .041)
presence of lymphatic vascular invasion (P
Usually follows involvement in the high axillary lymph nodes or IMN’s depending on the location of the primary lesion Predictive factors: High histologic grade >4 positive nodes Axillary level II or III involved nodes
Supraclavicular spread
Mammography
National Cancer Institute, American Cancer Society, and the American College of Radiology recommendation:
baseline mammogram at the age of 35 years (30 years in high-risk groups)
Repeat examinations should be carried out every 2 years beginning at 40 years of age.
In women older than 50 years, mammograms should be performed annually
complementary tool to mammography for the diagnosis of breast cancer
NCCN recommends ultrasound for those women presenting with a dominant mass or asymmetric thickening or nodularity
Ultrasound
potential limitation of _____ is that it provides cytology and no tissue architecture. Therefore, while the presence of malignant cells can be detected, cytology from fine-needle aspiration cannot conclusively differentiate invasive from noninvasive disease. However, for lesions that are palpable or easily visualized on ultrasound, this method results in rapid and efficient diagnosis
fine-needle aspiration
True or false?
Clinically node-negative patients have pathologic involvement in 10% to 40% of cases (depending on primary tumor size), whereas no pathologic evidence of tumor is found in 25% to 30% of patients with clinically palpable axillary nodes.
True
Small clusters of cells not greater than 0.2 millimeters
Nonconfluent
Nearly confluent clusters of cells not exceeding 200 cells in a single histologic lymph node cross section
Isolated tumor cells
defined by presence of either:
disseminated tumor cells detectable in bone marrow, circulating tumor cells, or found incidentally in other tissues (such as ovaries removed prophylactically) if not exceeding 0.2 millimeters.
new M0(i+) category
Defined as the extension of cancer cells beyond the basement membrane into the adjacent tissues with no focus more than 0.1 cm in greatest dimension
T1mic
Microinvasive
most common type of breast cancer, comprising more than 50% of all cases
Appears as solid cords or groups of ductal tumor cells varying in size and cytoplasmic content and degree of differentiation
Invasive or infiltrating
nonaggressive growth pattern, with an excellent prognosis
frequency of nodal metastasis of 13.8%
Tubular carcinoma
Prognosis, in general, is better than for other tumors
frequently seen in younger women and are commonly associated with patients with BRCA1 mutations
Medullary carcinoma
tend to be aggressive and multicentric and are prone to development of distant metastases
“mammographically silent,” meaning its detection or the full appreciation of extent of disease is often not visualized mammographically
much more commonly ER-positive than invasive ductal carcinoma
Lobular invasive carcinoma
observed in older women with relatively long duration of symptoms
slowly growing with a pushing border and has a low frequency of axillary lymph node metastasis
survival is appreciably better than with invasive ductal carcinoma
Mucinous carcinoma
rarely found in the breast
features and clinical behavior are similar to its counterpart in the salivary gland and the upper respiratory tract
Adenocystic carcinoma
characterized by growth of tumor cell clusters in prominent clear spaces resembling dilated angiolymphatic vessels
Invasive micropapillary carcinoma
relatively rare
increased expression of EGFR (HER1) provides an opportunity for targeted tumor therapy in these tumors.
Metaplastic carcinoma
cytokeratin markers but variable staining with neuroendocrine markers
histologic type and prognosis are identical to those of lung cancer
to distinguish these lesions from metastatic lung tumors or direct invasion of breast by Merkel cell carcinoma, lymphoma, or carcinoid tumor
reasonable to treat these patients with aggressive multiagent chemotherapy, excision of the primary tumor, and breast irradiation, although no data are available on the outcome of this approach.
Primary neuroendocrine small cell carcinoma
involvement of the nipple by tumor
Breast conserving surgery followed by radiation is effective in this disease
Paget’s disease
usually a benign lesion
tumors are large; usually they are encapsulated, without invasion of the adjacent breast
have a long initial period of slow growth followed by a sudden, rapid increase in size
grade (mitotic rate), surgical margins, and proliferative index have prognostic importance
Cystosarcoma phyllodes
variant of metaplastic carcinoma, includes a wide spectrum of lesions with mildly atypical features that may resemble fasciitis, fibromatosis, or myofibroblastic tumors
Unlike spindle cell carcinomas in general, they have no propensity for distant metastasis and should be termed tumors rather than carcinomas
Spindle cell carcinoma of the breast
In a review of MRI in the
management of breast cancer, Hylton summarized the poten-
tial for the current use of MRI:
the current use of MRI:
to complement mammography
in screening;
for differential diagnosis of questionable findings
on physical examination, mammography, and ultrasound;
assessment of response in the neoadjuvant treatment of breast
cancers
Bone scans are more commonly recommended:
in patients with stage II larger tumors (>3 cm) aggressive histopathologic features stage III or IV cancer.
Category I prognostic factors?
tumor size lymph node status micrometastasis histologic grade mitotic count hormonal-receptor status
Category II Prognostic factors?
HER2/neu expression
p53 mutations
lymphovascular invasion
DNA ploidy
Category III prognostic factors?
tumor angiogenesis EGFR transforming growth factor Bcl-2 cathepsin D overexpression
strongest predictor of distant metastasis and disease-free and overall survival
Tumor size
Nodal status
strongest predictor of disease-free and overall survival and is the primary factor that governs breast cancer staging
Axillary nodal status
the number of axillary nodes involved and the risk of dis-
tant metastasis, the most commonly employed schema is to
group patients into four prognostic categories namely:
node negative
1 to 3 involved nodes
4 to 9 involved nodes
more than 10 involved nodes
tubular, mucinous, and medullary subtypes have been shown to have a more favorable prognosis, compared with invasive ductal
invasive lobular tumors appear to have a prognosis similar to invasive ductal tumors
Poor prognostic categories include metaplastic, undifferentiated, and other rarer subtypes
Tumor Type
utilizes mitotic index, differentiation, and pleomorphism, each with scores of 1 to 3. Scores of 3 to 5 are well differentiated, 6 to 7 moderately differentiated, and 8 to 9 poorly differentiated
Elston and Ellis244 of the Nottingham group refined this methodology
Scarff-Bloom-Richardson classification system
True or false?
Tumors that express both ER and PR have the greatest benefit from hormonal therapy, but those containing only ER or PR still have significant responses.
True
Overexpression of the protein is associated with tumor aggressiveness and decreased disease-free survival in node-positive patients, with variable prognostic significance among node-negative patients
Her2/Neu
breast can extend from the midline to near the midaxillary line and cranial caudally from the ________
second anterior rib to the sixth anterior rib
