Breast Cancer Flashcards
(93 cards)
1
Q
Signs/symptoms - Early BC may be …?
A
Asymptomatic, and pain and discomfort are typically NOT present.
2
Q
If a lump is discovered, the following may indicate the possible presence of BC:
A
- Change in breast size or shape.
- Skin dimpling or skin changes.
- Recent nipple inversion or skin change, or nipple abnormalities.
- Single-duct discharge, particularly if blood-stained.
- Axillary lump.
3
Q
Diagnosis:
A
BC is often first detected as an abnormality on a mammogram before it is felt by the patient or health care provider.
4
Q
Evaluation of BC includes the following:
A
- Clinical examination.
- Imaging.
- Needle Bx.
5
Q
The following physical findings should raise concern:
A
- Lump or contour change.
- Skin tethering.
- Nipple inversion.
- Dilated veins.
- Ulceration.
- Paget disease.
- Edema or peau d’orange.
6
Q
If a palpable lump is found and possesses any of the following features, BC may be present:
A
- Hardness.
- Irregularity.
- Focal nodularity.
- Fixation to skin or muscle.
7
Q
Screening modalities for BC:
A
- BSE.
- Clinical exam.
- Mammography.
- U/S.
- MRI.
8
Q
U/S + MRI are more sensitive than mammo for …?
A
INVASIVE Ca in NON FATTY BREASTS.
9
Q
Bx:
A
Core Bx with image guidance is the recommended diagnostic approach for newly diagnosed BC.
*Can eliminate need for additional surgeries.
10
Q
Management - General:
A
- Surgery + RT, along with adjuvant hormone or chemo when indicated = Primary Tx.
- Surgery = lumpectomy or total mastectomy.
- RT may follow surgery in an effort to eradicate residual disease while reducing recurrence rates.
11
Q
2 General approaches for delivering RT:
A
- External-beam radiotherapy (EBRT).
2. Partial-breast irradiation (PBI).
12
Q
Standard Tx for DCIS:
A
Surgery +/- RT.
13
Q
Pharmacologic agents in management:
A
Hormone therapy + Chemotherapy are the 2 main interventions for treating METASTATIC breast cancer.
14
Q
Common chemo regimens include:
A
- Docetaxel.
- Cyclophos.
- Doxorubicin.
- Carboplatin.
- MTX.
- Trastuzumab.
15
Q
2 SERMS are approved for REDUCTION OF BC RISK IN HIGH-RISK WOMEN:
A
- Tamoxifen.
2. Raloxifene.
16
Q
In pts receiving adjuvant AI for BC who are at high risk of fracture, what do we give?
A
- Denosumab.
- Biphosphonates = Zolendronic acid, pamidronate.
+ Along with Ca + VitD.
17
Q
Background - The general approach to evaluation of breast cancer has been formalized as TRIPLE ASSESSMENT:
A
- Clinical exam.
- Imaging (mammo, u/s, both).
- Needle Bx.
18
Q
Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for …?
A
35-72% of the decrease in mortality.
19
Q
BC pathophysiology - Etiopathogenesis - Genomic profiling has demonstrated the presence of …?
A
Discrete breast tumor subtypes with distinct natural histories and clinical behavior.
==> These generally align with the presence of ER, PR , HER2.
20
Q
Evidence from the The Cancer Genome Atlas Network (TCGA) confirms the following 4 main breast tumor subtypes, with distinct genetic and epigenetic aberrations:
A
- Luminal A.
- Luminal B.
- Basal-like.
- Her2(+).
21
Q
Luminal A:
A
ER(+) +/- PR(+) + HER2(-).
- MC subtype.
- Less aggressive.
- Low grade.
- Good prognosis.
- Hormone responsive.
- Increasing age.
22
Q
Luminal B:
A
ER(+) +/- PR(+) + HER2(+).
- Similar to luminal A.
- More frequently ER(+)/PR(-).
- Worst outcome than Luminal A.
23
Q
Her2(+) (ER-):
A
- Less common, highly aggressive subtype.
- High grade.
- Risk at young age (<40) greater than luminal subtypes.
- African American may be a risk factor.
- Outcome improved with HER2.
24
Q
Basal-like:
A
Triple Negative, cytokeratin 5/6(+), and/or EGFR(+).
- Aggressive subtype.
- High grade.
- High mitotic rate.
- Risk at <40.
- More likely premenopausal African American women.
25
It is noteworthy that the basal-like BC subgroup shares a number of molecular characteristics common to ...?
Serous ovarian tumors, including the types + frequencies of genomic mutations.
**These data support the evidence that some breast cancer share etiologic factors with ovarian cancer.
**Most compelling are the data showing that pts with basal-type breast cancers show Tx responsiveness similar to that of ovarian cancer pts!
26
Various types of BC by percentage of cases:
1. IDC, tendency to metastasize via lymphatics. (75% of cases)
2. Over the past 25y, the LCIS incidence has DOUBLED (currently 2.8/100.000). Peak is 40-50y.
3. ILC (<15% of inv BC).
4. Medullary BC 5% of cases, generally younger women.
5. Mucinous (colloid) BC seen in <5% of inv BC cases.
6. Tubular BC (1-2%).
7. Papillary BC (>60, 1-2%).
8. Metaplastic BC (<1%, 6th DECADE, high in blacks).
9. Mammary Paget disease (1-4%), 6th DECADE (mean age 57y).
27
Etiology - Age:
1. Sporadic BC <40 is uncommon.
2. SEER data ==> Incidence <50 = 44/100.000. Incidence >50 = 345/100.000.
3. Bimodal ==> First peak at 50. 2nd peak at 70.
**May reflect the influence of age within the different tumor subtypes; poorly diff, high grade EARLIER, hormone-sensitive, slower-growing tumors LATER.
28
Etiology - Family Hx of breast cancer:
(+) FHx = the most widely recognized risk factor for BC.
1. Lifetime risk is up to 4x if a mother/sister are affected.
2. Up to 5x if 2 or more 1o relatives are affected.
3. Also greater risk if 1o relative was diagnosed <50y.
* despite FHx, many of these families have normal genetic testing results.
29
Etiology - A FHx of ovarian cancer:
In a 1o relative, especially if the disease occurred at an early age (<50y) ==> 2x the risk.
*often reflects inheritance of a pathogenic mutation in the BRCA1 or BRCA2 gene.
30
The FHx characteristics that suggest increased risk of cancer:
1. 2 or more relatives with breast OR ovarian cancer.
2. BC occurring in an affected relative younger than 50y.
3. Relatives with both BC + Ovarian Cancer.
4. 1 or more relatives with 2 cancers (BC and OC or 2 independent cancers).
5. Male BC.
6. BRCA1/BRCA2.
7. Ataxia telangiectasia heterozygotes (4x).
8. Ashkenazi Jews (2x).
31
A small percentage of pts, usually with a strong FHx of other cancers, have cancer syndromes:
1. PTEN.
2. TP53.
3. MLH1, MLH2.
4. CDH1.
5. STK11.
32
To aid in the identification of mutation carriers of BRCA1/2, a number of FHx-based risk assessment tools have been developed for clinical use, including the following:
1. BRCAPRO.
2. Couch.
3. Myriad I and II.
4. Ontario Family History Assessment Tool (FHAT).
5. Manchester.
**All of these assessment tools are highly predictive of carrier status and aid in reducing testing costs for the majority of mutation negative families.
33
BRCAPRO:
Most commonly used model, identifies approx 50% of mutation negative families, avoiding unnecessary genetic testing, and fails to screen only about 10% of mutation carriers.
34
Notably, a significant portion of ovarian cancers NOT previously considered familiar can be attributed to BRCA1/2 mutations. This has led to the suggestion that ...?
Women with nonmucinous invasive ovarian cancers may benefit from genetic testing to determine mutation status independent of a strong history or no history of BC.
35
Etiology - Reproductive factors and steroid hormones:
1. Late age at pregnancy.
2. Nulliparity.
3. Early onset of menses.
4. Late age of menopause.
*prolonged exposure to elevated levels of sex hormones has long been postulated as a risk factor for developing BC.
36
A number of epidemiologic and pooled studies support an elevated risk of breast cancer among women with high ...?
ESTRADIOL LEVELS.
The Endogenous Hormones and Breast Cancer Collaborative Group (EHBCG) reported a RR of 2.58 among women in the TOP QUINTILE of E2 levels.
37
Upon thorough review of the collective data, the Breast Cancer Prevention Collaborative Group (BCPCG) prioritized additional factors that might be included in the validation phase of a risk prediction model and gave high priority score to ...?
Free plasma E2 levels.
38
At present, routine measurement of plasma hormone levels ...?
IS NOT RECOMMENDED in the assessment of BC risk.
39
Role of OCPs + HRT:
The overall evidence suggests an approx 25% greater risk of BC among current users of OCPs.
==> The risk appears to decrease with age and time since OCP discontinuance.
40
For OCP users, risk returns to that of the average population risk about ...?
10 years after cessation.
41
Use of post-menopausal HRT:
Data obtained from case-control and prospective cohort settings support an increased risk of BC incidence and mortality with the use of postmenopausal HRT.
**Positively associated with length of exposure, with greater risk being observed for hormonally responsive lobular, mixed ductal-lobular, and tubular cancers.
**Risk is greater among women taking combination HRT than among those taking ESTROGEN-ONLY formulations.
42
In the Women's Health Initiative (WHI) trial, the incidence of invasive BC was ...?
26% HIGHER in women randomly assigned to combination HRT than in those assigned to placebo.
43
In contrast, the use of estrogen (conjugated equine estrogen) alone in women who had undergone ...?
Hysterectomy was associated with a 23% (but not significant) decrease in BC risk in comparison with placebo at initial reporting.
44
On extended follow-up (median, 11.8y), estrogen-only Tx for 5-9y in women with hysterectomy was associated with ...?
A significant 23% REDUCTION in the annual incidence of inv BC (0.27%; placebo, 0.35%).
**Fewer women died of BC in the Estrogen-only arm.
==> These findings CONTRAST with those reported from large observational case-control and prospective cohort studies, where estrogen alone was associated with increased risk (though the increase was consistently less than that associated with combined HRT use).
45
To aid the medical community in the application of HRT, a number of agencies and groups have published recommendations for HRT use in the Tx of menopause and associated bone loss.
At present, ...?
HRT IS NOT RECOMMENDED for prevention of cardiovascular disease or dementia or, more generally, for long-term use to prevent disease.
46
Guidelines for HRT in women at high risk for BC (ie, women with a FHx of BC, a personal history of BC, or benign breast disease):
None.
Only a few studies have evaluated the effect of HRT after a Dx of BC.
**The largest of these, the HABITS (Hormonal replacement therapy After Breast cancer-is IT Safe?) was stopped early because unacceptable rates of breast cancer recurrence and contralateral disease with 2y of HRT use (Hazard ratio, 3.5).
47
In another randomized clinical trial, ...?
NO increase in the risk of BC recurrences was observed in women at a median follow-up of 4.1y.
**use of progesterone-containing HRT was limited by intermittent use, with continuous exposure avoided.
48
Combination formulation containing estrogen + progesterone are contraindicated in women with a prior Hx of ...?
1. Inv BC.
2. DCIS/LCIS.
3. Strong FHx.
**This poses a significant challenge when confronted with a patient suffering severe menopausal symptoms.
49
Many new Tx for menopausal symptoms have been suggested:
1. Clonidine.
2. Venlafaxine.
3. Gabapentin.
4. Combination venlafaxine + gabapentin.
50
Etiology - Prior breast health history:
1. History of BC ==> 3-4X higher risk of a 2nd primary BC in the CONTRALATERAL breast.
2. DCIS/LCIS ==> 8-10X.
3. Bx positive for hyperplasia, FA with complex features, sclerosing adenosis, solitary papilloma ==> 1.5-2X.
4. ADH/ALH, especially if <45y, ==> 4-5X. Rises to 8-10X among women with MULTIPLE FOCI OF ATYPIA or CALCIFICATIONS in the breast.
***Benign lesions, including FCD, such as fibrocystic change without proliferative breast disease or FA, have not been associated with increased risk.
51
Etiology - Lifestyle risk factors:
5X difference between Eastern Africa and Western Europe.
==> Adherence to the mediterranean diet ==> Lower risk for BC ==> In particular, for types of BC that carry a poorer prognosis in postmenopausal women.
52
Compared with women who reported the least adherence to a Med diet, women who most closely adhered to the diet has a ...?
40% reduction risk for ER(-) BC (HR 0.60; ptrend = 0.032).
+
39% reduced risk for PR(-)/ER(-) disease (HR 0.61; ptrend=0.047).
==> The study found no significant associations with the diet and the risk of ER(+) disease or total BC risk.
53
Etiology - Obesity:
Incr. risk of post-menopausal BC has been consistently associated with the following:
1. Adult weight gain of 20-25kg above body weight at age 18.
2. Western diet.
3. Sedentary lifestyle.
4. Regular, moderate consumption of alc (3-5/per wk).
54
The western lifestyle (ie chronic excess energy intake from meat, fat, and carbs + lack of exercise) strongly correlates with:
1. Obesity, particularly ABDOMINAL OBESITY.
2. Chronic hyperinsulinemia.
3. Higher production and availability of IGF-1.
4. Incr. levels of endogenous sex hormones through SUPPRESSION of SHBG.
55
Studies of dietary fat, total energy, and meat intake levels have largely been inconsistent in population studies of adult women with regard to risk of BC.
In contrast, epidemiologic studies have more consistently found ...?
A POSITIVE relation between BC risk and early-life exposures such as diet, obesity, and body size (including HEIGHT).
**The mechanism of this relation is unknown.
56
Etiology - Environmental risk factors:
Many have been investigated:
1. Tobacco smoke (both active and passive).
2. Dietary (eg charred and processed meats).
3. Alc consumption.
4. Environmental carcinogens (eg exposure to pesticides, radiation, and environmental and dietary estrogens).
Of these ==> ONLY HIGH DOSES OF IONIZING RADIATION to the chest area, particularly during puberty, have been unequivocally linked with an increased risk of BC in adulthood.
57
A pt treated for HL with Mantel radiation that includes the breasts in the radiation field has a ...?
5X risk of developing BC.
==> This risk increases markedly for women treated during adolescence, evidence suggests that cumulative risk increases with age as a function of age of exposure and type of therapy.
58
Epidemiology - New cases in 2017:
Approx. 252,710 new cases of female inv BC.
Along with 2470 cases in men.
+ 63,410 new cases of in situ BC, approx 83% of these cases are expected to be DCIS, and 12% are expected to be LCIS.
59
Incidence over the period 1987-1999 varied dramatically by histologic type:
1. Common ductal carcinomas increased modestly from 1987-1999, whereas invasive lobular and mixed ductal-lobular carcinomas increased dramatically during this time period.
2. For women <50, BC rates have remained stable since the middle to late 1980s.
3. Rates of DCIS have stabilized since 2000.
60
Whereas a decline in inv BC was evident as early as 1999, rates dramatically DECREASE ...?
In women aged 50 or older between 2001-2004.
During the same period, no significant change was observed in the incidence of ER(-) cancers or cancers in women younger than 50y.
**The decline in rates from 2001-2004 was greater between 2002 and 2003 and was limited to non-Hispanic whites.
61
The reason for the decline has been extensively debated. What is the primary explanation?
The near-immediate decrease in the use of combination HRT for menopausal symptoms.
62
However, Jemal and Li argued that the decline in BC incidence started earlier than the reduction in combination HRT and that the decline is ...?
Due in part to a "SATURATION" in mammographic screening mammography that produced a plateau in incidence when such screening stabilized in the late 1990s.
==> Saturation of the population would be predicted to reduce the pool of undiagnosed or prevalent cases.
63
For women aged 69y or older, BC rates started to decline as early as ...?
1998 ==> when screening first showed a plateau.
**this observation is consistent with the prediction that if widespread screening + earlier detection are effective, they should result in a peak incidence among women during the 6th and 7th decades of life, followed by a decline.
==> this is exactly the pattern now being reported for screened populations.
64
The 2nd observation noted by Jemal et al was that despite evidence for ...?
A plateau effect, screening saturation alone could not explain the dramatic declines or the pattern of decline.
==> the decline in incidence was only for ER(+) tumors and not for ER(-) ones.
==> These findings support the competing hypothesis that exposure to HRT as estrogen in combination with synthetic progesterone promoted the growth of undetected tumors.
65
Under this scenario, withdrawal of combination HRT at the population level may have resulted in regression or a slowing of tumor growth.
The latter, it has been argued, would result in a delay in detection.
OVERALL, ...?
Incidence figures from 2005-2009, for which the most recent data are currently available, suggest that overall new BC case rates have remained FAIRLY STABLE since the initial drop.
66
It is notable, however, that the annual percentage change from 2005 to 2009 ...?
INCREASED IN WOMEN 65-74y by 2.7% during this period.
==> Rates that parallel 2001 incidence figures for this age group.
==> This rise occurred in spite of very low use of HRT by this population + suggests that the drop in combination HRT use immediately after 2002 may not have resulted in a sustained decrease in new BC cases.
67
At present, it is UNCLEAR whether decreased use of combination HRT ...?
Has resulted in a SUSTAINED reduction in the incidence of BC at the population level OR has shifted the age at which preexisting disease would become detectable.
==> Longer-term follow-up of post-2002 trends in relation to combination HRT use are needed to address this question.
68
Epidemiology - Age-related demographics:
1. 5/100.000 in women 20-24y.
421. 3/100.000 in women 75-79y.
95% of new cases occur in women aged 40y or older.
**the median age of women at the time of BC diagnosis is 61y.
69
Age-related demographics - Rates of in situ BC ...?
STABILIZED among women 50y and older in the late 1990s; this is consistent with the proposed effects of screening saturation.
==> However, the incidence of in situ BC continues to increase in younger women.
70
Epidemiology - Race- and ethnicity-related demographics:
The incidence of BC is higher in non-Hispanic whites than in women of other racial and ethnic groups.
**among women younger than 40y, African American women are diagnosed with larger, advanced-stage tumors (>5cm) and are more likely to die of BC at every age.
71
According to the American Cancer Society (ACS), BC rates among women from various racial and ethnic groups are as follows:
1. Non-Hispanic white ==> 128.1/100.000.
2. African American ==> 124.3/100.000.
3. Hispanic/latina ==> 91/100.000.
4. American Indian/Alaska Native ==> 92/100.000.
5. Asian American/Pacific Islander ==> 88/100.000.
72
According to the American Cancer Society (ACS), DEATH RATES from BC among women from various racial and ethnic groups are as follows:
1. Non-Hispanic Whites ==> 22/100,000.
2. African American ==> 31/100,000.
3. Hispanic/latina ==> 14.5/100,000.
4. American Indian/ Alaska native ==> 15/100,000.
5. Asian American/ Pacific Islander ==> 11.4/100,000.
73
BC death rates wre ...% HIGHER in black women than white women.
42%.
74
Prognosis - BC mortality fell by ...% between 1990 and 2000 for women aged 30-79y.
24%.
75
The largest decrease in mortality has been seen in women ...?
Younger than 50y (3.3% per year), compared to those aged 50y or older (2.0% per year).
76
The 2017 estimates are ... expected BC deaths.
41,070 = 40,610 in women + 460 in men.
77
BC prognostic factors include:
1. Axillary LN status.
2. Tumor size.
3. Lymphatic/vascular invasion.
4. Age.
5. Grade.
6. Histologic subtype (eg tubular, mucinous [colloid], or papillary).
7. Response to neoadjuvant Tx.
8. ER/PR status.
9. HER2 gene amplification or overexpression.
78
Importance of axillary LN status:
SURVIVAL + RECURRENCE are independent of level of involvement but are directly related to the NUMBER OF INVOLVED NODES.
79
Pts with node-negative disease have an overall 10y survival rate of ...?
70%.
80
Pts with node-NEGATIVE disease have a 5y recurrence rate of ...?
19%.
81
In pts with node-positive disease, the recurrence rates at 5y are as follows:
1-3 nodes ==> 30-40% recurrence.
4-9 nodes ==> 44-70% recurrence.
10 or more nodes ==> 72-82% recurrence.
82
HER2-targeted Tx consists of the following:
1. Trastuzumab = Mab.
2. Pertuzumab = Mab.
3. Lapatinib = A small-molecule ORAL TKI.
4. Trastuzumab-emtansine = An ab-drug conjugate directed specifically to the HER2 receptor.
83
HER2 status has also been shown to predict response to certain chemotherapeutic agents:
1. DOXORUBICIN ==> Retrospectively analyzed results from clinical trials have shown that HER2(+) benefit from ANTHRACYCLINE-based regimens ==> perhaps because of the frequent COAMPLIFICATION of topoisomerase II with HER2 (!).
2. PACLITAXEL adjuvant ==> Preliminary data also suggest that HER2 positivity may predict response to and benefit from paclitaxel in the adjuvant setting.
84
Importance of LCIS:
Approx. 10-20% of women with LCIS develop inv BC within 15y after the LCIS dx.
==> BIOMARKER of incr. BC risk.
85
IDC and ILC prognosis:
Comparable prognosis.
86
Prognosis of medullary BC:
Typical or classic MBC is often associated with a GOOD prognosis, DESPITE the unfavorable prognostic features (ER neg, high grade, high proliferative states).
==> HOWEVER, an analysis of 609 MBC specimens from various stage I and II NSABP protocols indicates that overall survival and prognosis ARE NOT AS GOOD AS PREVIOUSLY REPORTED.
***ATYPICAL MBC also carries a poorer prognosis.
87
Overall, pts with mucinous carcinoma have ...?
An EXCELLENT PROGNOSIS, with >80% 10y-survival.
88
Tubular carcinoma - Prognosis:
Similar to mucinous ==> Low incidence of LN involvement and very high overall survival state.
89
Cystic papillary carcinoma - Prognosis:
Good ==> Low mitotic activity, indolent course.
90
Invasive micropapillary ductal ca - Prognosis:
Has a more aggressive phenotype, even though approx 70% of cases are ER(+).
91
A retrospective study of 1400 cases of IDC identified ...?
83 cases (6%) with at least one component of invasive MICROPAPILLARY ductal carcinoma.
92
METAPLASTIC BC - Prognosis:
1. The majority of published case series have demonstrated a worse prognosis than with IDC, even when adjusted for stage.
==> 3y overall survival rate of 48-71% and 3y disease-free survival rate of 15-60%.
2. In most case series, large tumor size and advanced stage have emerged as predictors of poor overall survival and prognosis.
***Nodal status does NOT appear to impact survival in METAPLASTIC BC.
93
Paget disease - Prognosis:
A/w underlying BC in 75% of cases.
Poor prognostic factors:
1. Palpable BC.
2. LN involvement.
3. Histologic type.
4. Age of less than 60y.
==> Paget with a palpable mass usually has an INVASIVE component and a lower 5y-survival rate (20-60%), compared to those who do not have palpable mass (75-100%).
