Breast Cancer Flashcards
What were the treatment groups and main outcome of the NSABP B-04 Trial?
Total mastectomy vs. total mastectomy + XRT vs. radical mastectomy. Outcome = no difference in DFS or OS.
What were the treatment groups and outcome for NSABP B-06 Trial?
Total mastectomy vs. lumpectomy vs. lumpectomy +XRT. Outcome = No difference in DFS or OS. Addition of XRT to lump reduced local recurrence from 39 to 10%
What were the treatment groups and outcome for NSABP B-13 Trial?
Surgery alone vs. surgery + adj chemo in N(-) patients with ER(-) tumors. Outcome= improved DFS for adj chemo group.
NSABP B-14?
Surgery alone vs. surgery +adj Tamoxifen in N(-) patients with ER (+) tumors. Outcome= Improved DFS for adj tamoxifen group. 10 years of tamoxifen offered no benefit over 5 yrs.
NSABP B-18?
Neoadj chemo with doxorubicin, CPA, or both x 4 cycles vs. the same regimen given postoperatively. Outcome = No difference in DFS or OS between groups.
NSABP B-21?
Lumpectomy + tamoxifen vs. lumpectomy + tamoxifen +XRT vs lumpectomy +XRT for N(-) tumors <1 cm. Outcome = Combination of XRT and tamoxifen was more effective than either alone in reducing ipsi-lateral breast tumor recurrence.
NSABP B-27?
Neoadjuvant chemo comparing AC x 4 cycles then surgery vs. AC x4 cycles, docetaxel x 4 cycles then surgery vs. perioperative chemo (surgery between 4 cycles of AC preop and 4 cycles docetaxel postop). Outcome= four cycles of AC + docetaxel neo-adjuvantly better than the other two.. Addition of docetaxel to AC increased the clinical CR rate by 50% and nearly doubled the pCR compared to to AC alone.
NSABP B-32?
SLB biopsy followed by axillary dissection vs. SLN biopsy alone for clinically N(-) patients. Outcome= SLN identification rate was high for both, negative predictive value was high for both.
ACOSOG Z011?
Clinically N(-) T1T2 cancer with 3 or fewer sentinel nodes with mets on histology. Randomized to no further treatment vs. ALND. At 5 years, no difference in OS or DFS in SLN-only group. Closed d/t poor accrual. Suggested that clinically N(-) patients who will receive WBRT and adj chemo DON’T need ALND to improve survival. Doesn’t apply to neoadjuvantly treated px or partial radiation or prone radiation)
Indications for adj chemo?
> 1cm, positive LN, risk of distant recurrence >10%, some hi risk features (LVI, triple neg, HER2, morphology)
Evidence for adjuvant chemo?
EBCTCG meta-analysis (Early BC trialists collaborative group)–> 2005, 60 RCTs comparing chemo to none. 10-15 yr benefits in recurrence and mortality, esp for younger women, similar N(-) and N(+) for mortality but greater for N(+).
Is adj chemo equally beneficial for ER(-) vs. ER(+) tumors?
CALGB trials in px with N(-) cancer indicated greater chemotherapy benefit i ER(-) tumors. But it’s beneficial to both groups in subgroup analysis of the EBCTCG meta-analysis.
Website to help with decisions re: adjuvant therapy?
Adjuvant! Online (www.adjuvantonline.com) estimates recurrence and mortality, independently validated by Canadian investigators, results within 1% of actual recurrence/mortality rates.
What is and who gets Oncotype Dx?
RT-PCR assay for HR(+) N(-) patients who will receive 5 yrs tamoxifen. Measures gene expression of 16 cancer-related gens including ER, PR, ER2, Ki67; uses regression model to calculate a recurrence score to estimate distant mets at 10 yrs.
What suggested cut-off points categorize patients based on Oncotype Dx? And what are their associated risk of distant recurrences at 10 yrs?
Low risk (RS<18), Intermediate (RS 18-31), high (RS >31)…correspond to 6.8%, 14.3%, and 30.5% risk of distant mets.
What is the TAILORx trial?
Randomized patients with HR(+) N(-) cancer and intermediate RS to chemo and endocrine therapy vs. endocrine therapy alone.
What is Mammaprint?
FDA-approved 70-gene signature developed in the Netherlands from a retrospective series of 78 patients who received no adj systemic therapy, had <5 cm N(-) cancer, age <55. This assay stratifies patients in good and poor risk grps according to the risk of developing a distant mets.
What clinical trial will test Mammaprint?
MINDACT (microarray in N(-) dz may avoid chemotherapy) trial.
What did the EBCTCG meta-analysis show regarding chemotherapy regimen for adj chemo?
That anthracycline-containing regimens (doxorubicin, epirubicin) were superior to classic CMF (CPA, MTX, FU). Anthra-based regimens x 6 months reduced annual death rate by 38% for women <50 yo and by 20% for age 50-69.
What is optimum dose for doxorubicin and epirubicin? What is the incidence of CHF for each and at what cumulative doses?
Doxo–60 mg/m2, 1.6% at cumulative dose of 240 mg/m2.
Epi–100 mg/m2, 2.1% at cumulative dose of 360 mg/m2.
Why do anthracyclines especially benefit HER2 positive patients?
recent meta-analysis reported higher benefit in DFS in HER2+ vs HER2- dz. Co-amplification of TOP2A (topoisomerase) and her2 is underlying mechanism. Both on chrome 17.
What is BCIRG 006 trial?
Randomized HER2+ to trastuzumab-containing regimen + or - anthracycline. Reported similar efficacy for both.
What did EBCTCG overview analysis say about taxanes?
Randomization to a taxane containing regimen improved RFS. Several meta-analyses have seen small but significant improvements in DFS and OS (5 and 3%, respectively)
What did the ECOG 1199 study show?
Provided evidence that scheduling of taxable treatment is important. 5000 patients with N+ tumors were randomized to 4 diff taxane groups. Improvements in OS were seen for weekly paclitaxel and 3 weekly docetaxel vs. pacitaxel given every 3 weeks. Heme toxicity with weekly docetaxel.
What are the 4 distinct molecular subtypes of breast cancer?
basal like, HER2-enriched, luminal A, and luminal B. In general, basal like and HER2+ are ER-neg. and Luminal subtypes are ER+. The triple-neg are usually basal-like (but this misclassifies 30% of basal-likes)
What are Luminal A characteristics, usually?
ER-pos, Oncotype Dx low RS, Mammaprint good risk, low Ki67 expression, low grade.–> high likelihood of benefitting from endocrine therapy.
