Breast Cancer Pearls
1. Subtypes with a more favorable prognosis include breast cancers
with tubular, mucinous, papillary, or cribriform features
2. On the basis of the most recent Early Breast Cancer Trialist’s
Collaborative Group findings, improved local control at 5 years results in a
proportional improvement OS at 15 years. This was true whether improved local
control was obtained by more extensive surgery or the addition of radiation.
3. The EFECT trial compared Fluvestrant and Exemestane in
postmenopausal women progressing on a nonesteroidal AI. Response rate, clinical
benefit, and TTP were identical; suggesting either Fluvestrant or Exemestane
would be reasonable options. However, the EFECT trial used a loading dose of
Fluvestrant (500 mg on day 0, 250 mg on days 14 & 28, and then monthly) to
achieve steady-state potentially therapeutic levels within the 1st
month.
4. FNA can reliably diagnosis cancer but cannot distinguish DCIS
from invasive disease. The false negative rate is 5% to 10% for FNA but less
than 4% for core biopsy. In a prospective study of 1550 patients undergoing
biopsy for mammographic abnormalities, core biopsy reduced the number of
surgical procedures.
5. The IES trial is a randomized trial of Exemestane after 2 to 3
years of Tamoxifen therapy in postmenopausal women with primary breast cancer
and it showed that DFS was improved by 24%, and time to contralateral breast
cancer was reduced by 43%. Although OS was not improved in the entire study
population, analysis of patients with known ER+ disease did find significant
improvement in survival.
6. Li-Fraumeni syndrome is characterized by breast cancer, soft
tissue sarcoma, CNS tumors, adrenal cancer, Leukemia, and prostate cancer.
7. The addition of Lapatinib to Capecitabine in patients with
advanced HER2+ breast cancer increased TTP (HR 0.49; p<0.001). To date there
is no OS improvement. Diarrhea and rash were significantly more frequent in
patients receiving combined therapy
8. PARP1 is a cellular enzyme involved in the single-strand DNA
repair through the base excision repair. Since both BRCA1 and BRCA2 are
important in DNA repair, patients with BRCA1 & BRCA2 mutations may be
sensitive to PARP inhibition.
9. It is not clear that early detection of distant metastatic
disease improves clinically important outcomes. As such, screening mammography
is the only imaging study recommended for routine surveillance in asymptomatic
patients.
10. In the NSABP B-20 trial, the addition of chemotherapy to
Tamoxifen didn’t improve distant recurrence free survival at 10 years in
patients with OncotypeDX assay of low or intermediate recurrence score. However
in patients with high recurrence score, the distant recurrence free survival at
10 yrs improved from 60% to 82% (22%) with the addition of CMF.
11. The factors associated with an increased relative risk above 4
for the development of breast cancer include BRCA mutations, Lobular carcinoma
in situ, atypical hyperplasia, and radiation exposure before the age of 40.
CHEK2 mutations, mammographic breast density are associated with a relative
risk between 2 & 4.Hormonal risk factors have relative risks of less than
2.
12. Approximately 10% of all breast cancers are associated with germ
line mutations, while other 90% occur sporadically.
13. In the ACOSOG Z10 trial, increasing age, body mass index, and
surgical sites with fewer than 50 patients enrolled were associated with a
decrease in sentinel node identification rate.
14. Adjuvant Tamoxifen results in an improvement in OS for at least
15 years. The benefits are independent of age, menopausal status and the use of
chemotherapy.
15. DCSIS is most common among women ages 49 to 69 yrs. Several
studies have reported an increased risk of local recurrence in younger women.
Initial studies suggested that MRI can both over and underestimate the extend
of DCIS and doesn’t improve surgical planning.
16. DCIS is primarily a local disease with excellent prognosis, and
axillary node dissection is not necessary.
17. Inflammatory breast cancer is a clinical diagnosis. Dermal lymphatic
invasion on full thickness skin biopsy is often seen but is not required for
diagnosis. Most women will have lymph node involvement. In the absence of
distant metastases, inflammatory breast cancer is staged as T4d, stage IIIC
disease.
18. BRCA1 associated breast cancer usually occur in younger women,
have aggressive features and are characterized by a triple negative phenotype
19. Approximately 80% of cases of male breast cancer are ER+,
presumably because men are effectively postmenopausal.
20. The use of RT after BCS for DCIS reduces both invasive and
noninvasive recurrences but doesn’t alter OS.
21. BRCA1 is the gene at locus 17q21, BRCA2 is the gene at locus
13q12.3, P53 is the gene at locus 17q13.1
22. Skin sparing mastectomy does not alter the risk of local recurrence.
Contrary to initial concerns, immediate reconstruction does not alter the risk
of local recurrence, limit ability to detect local recurrence, or delay
initiation of systemic therapy. Although fat necrosis, fibrosis, and volume
loss are common with RT after autologous reconstruction, complete flap loss is
rare.
23. Gail model estimates a woman’s risk of developing breast cancer
on the basis of age at menarche, age of first live birth, number of previous
breast biopsies and presence of atypia, and the number of 1st degree
female relatives with breast cancer. It may underestimate the risk in women
with a strong family history because it doesn’t include 2nd degree
relatives, men with breast cancer, or relatives with ovarian cancer.
24. In the women’s Health Initiative Study, combined estrogen and
progestin increased the risk of developing breast cancer with a hazard ratio of
1.24. The increase in breast cancer was detected at 2 years, but an excess of
abnormal mammograms was apparent at 1 year. Hormone replacement therapy users
were more likely to have nodal involvement or distant metastases at diagnosis.
25. ASCO guidelines for MRI screening are in patients with a known
BRCA mutation, untested 1st degree relatives of BRCA mutation
carriers, or patients with an estimated 20% to 25% lifetime risk of breast
cancer (e.g., patients who received mantle radiation before age 40). There is
currently insufficient evidence to recommend for or against MRI screening for
patients with a personal history of breast cancer.
26. Intergroup trials (N9831 and B31) showed that adding trastuzumab
to adjuvant chemotherapy in resectable HER2+ breast ca improves DFS (50%),
distant DFS (50%), and OS (30%)
27. Absolute contraindications for BCS include pregnancy, more than
1 primary in different quadrants, and previous radiation to the breast.
28. The addition of Avastin to Taxol significantly prolonged PFS
(11.8 vs 5.9 months, HR 0.6, p<.001) and increased objective response rate
(36.9% vs. 21.2%, p<.001), but median OS was similar in both groups (26.7 vs
25.2 months; HR 0.88, p=.16)
29. In a recently reported phase III trial, the addition of
ixabepilone to capecitabine increased ORR but caused significantly more
neutropenia than capecitabine alone. Neutropenic fevers were uncommon but
increased as well.
30. Lapatinib is a dual EGFR and HER2 receptor inhibitor.
31. The relative benefits of chemotherapy are independent of age, ER
status, and use of hormonal therapy, Although the absolute benefits will differ
according to baseline risk
32. AIs lower estrogen levels by 90% in postmenopausal women. To
date, No study has shown a survival advantage, and the optimal duration of
therapy is unknown. AIs increase the risk of fracture during therapy, but that
risk appears to revert to baseline levels once therapy has been discontinued.
33. Pregnancy and lactation are contraindications to SNB.
34. An underlying malignancy is found in approximately 97% of
patients with Paget’s disease, frequently with high grade histology. Half of
cases are hormone receptor negative, consistent with the higher rate of
underlying high tumors.
35. In the P1 trial, Tamoxifen reduced the risk of breast cancer by
84% in patients with atypical hyperplasia. Although Raloxifene provided similar
benefits with a more favorable safety profile than Tamoxifen in the STAR trial.
This trial only included postmenopausal women. Oophorectomy before menopause
decreases the risk of breast cancer by 50% to 65% depending on age at the time
of surgery. Although bilateral mastectomy decreases the risk by more than 90%,
the risk is not completely eliminated.
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