Breast

Question 1

Breast cancer is the ___ most common cancer in women. it is the ___ in terms of cancer deaths.

Answer 1

1st most common cause of cancer in women. it is second in cancer deaths. lung cancer is 2nd common but the most deadly.

Question 2

what is a total mastectomy?
radical mastectomy?
modified radical mastectomy?

Answer 2

total: removal of breast tissue only. NO axillary dxn.
radical: pect major removed, levels I-II removed
modified radical: preservation of pec major, levels I-II removed
Halstead mastectomy, removes levels I-III and pec major.

Question 3

BRCA 1 and BRCA 2 have what % chance of developing breast cancer?

Answer 3

both have 60-80% risk . BRCA1 has 30-40% risk of developing ovarian ca. BRCA 2 is more commonly ER+ and associated with male breast cancer. nearly all male breast cancers are ER+

Question 4

What was the NSABP P2 STAR TRIAL?

Answer 4

randomized women s/p llumpectomy with IDC to tamoxifen vs raloxifene x 5 yrs in post menopausal women. incidence of invasive brca was same, 0.4%, but fewer noninvasive cases with tamoxifen. raloxifene had a reduced risk of uterine cancer, cataracts and VTE. but same osteoporotic fx, stroke and CAD.

Question 5

NSABP 04 randomzied cLN0 breast cancer to radical mastectomy vs total mastectomy+RT vs total mastectomy alone. If cLN+ then randomized to radical mastectomy vs total mastectomy+RT. is there a benefit to radical mastectomy as a result of this trial?

Answer 5

25yr f/u showed same DFS, OS, regardless of LN status, therefore, no benefit to radical mastectomy.
woemn who developed axillary disease then received axillary dxn. no adj tx given. RT was 50Gy to CW and 45Gy to IM and SCV LN. boost of 10-20Gy to those with +LN.

Question 6

NSABP 17 showed what?

Answer 6

Role of RT after lumpectomy in DCIS. pts s/p lumpectomy with negative margins with DCIS randomized to obs vs 50Gy(later a 10Gy bst was allowed). 15 yr f/u showed a nearly 50% reduction in noninvasive LF and invasive lF. (19->9%, and 16->9%). RT does not affect DM or OS.

Question 7

EORTC 10853, which features was associated with increased LR?

Answer 7

7%, invasive LF 13->8%. RT did not affect DM or OS.

Question 8

Per NSABP B24, tamoxifen did what?

33% were <50 yo.

Answer 8

32% risk reduction of invasive in breast tumor recurrence and contralateral events with the addition of tam to RT. 2/3 of the contralateral events were invasive. OS not improved. randomized many women with DCIS to lumpectomy, 50Gy and obs vs tam x 5 yrs. 25% had +margins, ER status unknown. invasive recurrences were fond to decrease overall mortality. however noninvasive recurrences did not decrease overall mortality.

Question 9

the UKCCR for DCIS showed what?

Answer 9

2x2 randomization for lumpectomy vs RT, tmx, both or neither. all breast events: 8%, 18%, 6%, 22%. unlike NSABP 24, there was no additional benefit of tamoxifen for ipsilateral invasive events, but it did decrease the DCIS incidence.
notably, UKCCR was a SCREENING enrollemnt study, therefore 10% of the women were <50 years old. likely contributing to the lack of benefit of tamoxifen or results.

Question 10

what was the ECOG 5194 study? (Hughes trial)

Answer 10

phase II observational DCIS study. low risk women with >=3mm margins after lumpectomy were obs. tamoxifen was allowed. cohort 1 low risk G1-2 <1cm. LF was 6% vs 15% in high risk.

Question 11

what is the difference between the ECOG 5194 and Wong /Harvard DCIS study?

Answer 11

Wong/Harvard study sought to determine the risk of IBTR after lumpectomy for low risk DCIS. margins were >=1cm, as opposed to 3mm in ECOG. tumors were <2.5cm and mostly G1-2 (6% were G3), so overall lower risk than the ECOG study. tamoxifen was NOT allowed on the Wong study. the 5yr IBTR was 12% and therefore closed early.

Question 12

what 4 features did the Van Nuys Prognostic Index for DCIS look at?

Answer 12

age (>60, 40-60, -1cm, 0.1-0.9cm, =4cm). Size, Grade necrosis and margins

Question 13

what are the definite contraindications for breast conserving therapy?

Answer 13

multicentricty (multiple foci in different quadrants. multifocal is multiple foci in same quadrant). prior breast/chest RT, pregnancy, persistently postiive margins on excision, diffuse suspicious or malignant appear microcalcs.

Question 14

what are the relative contraindications for breast conserving tx?

Answer 14

SLE or active connective tissue disease, tumors >5cm due to poor cosmetic outcome, focally positive margin, women <35 yo or premenopausal women with known BRCA mutation

Question 15

what do you do for LCIS?

Answer 15

LCIS increases the risk of developing invasive disease by 9-12 times. it is 25% at 20 yrs. this can reduced with tamoxifen, prophlactic mastectomy b/l. there is no role for RT in this disease.

Question 16

per NSABP B06 what did they find?

Answer 16

20 yr f/u showed RT decreased LR in the lumpectomy arm from 39% to 14%.
B6 randomized many women with stage I/II (<4cm) brca into : total mastectomy+ALND, lumpectomy+ALND or lumpectomy+ALND+50Gy. everyone had negatve margins, ER data was available for 75% with 66% being ER+. 62% were N- and N+ got adj melphalan+5FU. Same DFS, OS and DMFS. LR was scored as recurrence in CW or mastectomy scar but in lumpectomy failures, they were called cosmetic failures

Question 17

Milan I trial compared radical mastectomy (RM) vs quadrantectomy+60Gy. it showed what?

Answer 17

LC was better in the radical mastectomy arm, with no benefit to OS. T1N0 women randomized to RM vs quandrantetctomy+50GY, 10GY boost. 25% were LN+ and got CMF. 20yr LF was 2%(RM) and 9% BCT. same in quadrant recurrence and OS (41%) and DFS (75%).

Question 18

CALGB C9343 of tam vs tam+RT in old women >=70 with small tumors they found?

Answer 18

older women with small T1 tumors were randomized to tam or tam+RT. 97% were ER+. addition of radiation improved LF from 9% to 2%. but same in time to mastectomy and same OS (61%). Hughes trial.

Question 19

what did the 14yr f/u in the NSABP B21 trial comparing tmx vs RT vs txm+RT show in small T1 tumors?

Answer 19

1,000 women randomized with small <=1cm tumors. initial results at 8 yrs showed higher rate of LF with tmx alone, 16% and the lowest LF with RT+tmx, 3%. RT improved IBTR when compared to tmx alone. tmx did improve the incidence of contralateral br ca from 5.4% to 2.2%. survival was the same, mid-90s%.

Question 20

NSABP B18 showed what? this was a neoadj trial

Answer 20

1,500 women randomized to preop or postop chemo with AC. RT given after lumpectomy. no PMRT allowed. nejoadj chemo increased % of peopel getting BCS (68 vs 60%), there was no improvement in DFS or OS. pCR after neoadj AC was 13%. those with pCR did have *improved DFS and OS.

Question 21

NSABP trials name them:
4
6
17
18
21
24
27

Answer 21

4: IDC, +/-N1, 1-rad mast; 2-total mast+RT; 3-total mast. Showed no benefit to radical mast.
6: IDC, largish 14%.
17: DCIS. lumpectomy +/- RT, neg margins. 50% decrease in LF with RT. no change in OS or DM.
18: preop or postop AC with lump+RT. no improvedment in OS or DFS. pCR 13% and they had improved DFS and OS.
21: small tumor tumors randomized to tmx, RT or tmx+RT. RT improved LC. Tmx imrpoved IBTR and CBTR.
24: DCIS. lump+RT +/- tmx. Tmx dec IBTR and CBTR. same OS.
27: neoadj AC +/- T before or after surgery. the pCR improved with addition of T increased pCR from 26% from 13% without T. those with pCR had improved DFS and OS.

Question 22

what were the pCR rates of NSABP B18 and B27?

Answer 22

13% and 26%
B18 was neoadj AC, B27 was neoadj AC +/- T before or after surgery. addition of T did not improved DFS or OS, it did improve pCR rate to 26%, and therefore improved DFS and OS with pCR.

Question 23

what are Haagensen’s grave signs?

Answer 23

5 grave signs. skin ulceration, fixation of tumor to chest wall, axillary nodes >2.5cm, edema of >1/3 of the breast skin, fixed/matted axillary nodes.

Question 24

what are some characteristics of inflammatory breast cancer?

Answer 24

this is a clinical diagnosis and path confirmation of tumor in dermal lymphatics is not required. there is rapid onset with erythema, warmth & edema. there is a mass present in 50% of cases. even after CR after neoadj chemo, BCT is still contraindicated. 5% of women will have a normal mammogram.

Question 25

Danish 82b PMRT trial showed what?

Answer 25

1,700 PREmenopausal women had modified radical mastectomy with median of 7LN got adj CMF, CMF+RT or CMF+tmx(this one was stopped due to high mortality). RT was 48-50Gy to CW, SCV, axilla and IM nodes. RT decreased LRF from 32%->9% translating into a ~10% OS benefit at 10yrs (52->45%). DFS was also improved. most of the LF were at the CW.

Question 26

Danish 82c PMRT trial showed what?

Answer 26

1,400 POSTmenopausal women had modified rad mast (same as 82b) but randomized to tmx for 1 yr or tmx+RT. Same RT with 48-50Gy to CW, SCV, axilla and IM nodes. RT decreased LRF from 35%->8%, translating into ~10% OS benefit at 10 yrs (45->36%).

Question 27

What was the LRF improvement with RT in the 82band 82c trials? OS?

Answer 27

82b improved LRF from 32 to 9%
82c improved LRF from 35 to 8%
both had about a 10% improvement in OS

Question 28

The British Columbia PMRT showed what?

Answer 28

300 premenopausal women s/p modified rad mast with median of 11 nodes got CMF or CMF+RT. RT was 37.5Gy to the CW, SCV, axilla and IM nodes. RT improved LRF from 26 -> 10%, translating into 10% OS benefit at 20yrs 47 vs 37%. DSS improved with RT from 53 to 38%.
compared to Danish trials, BC trial used lower RT dose and had a smaller benefit with LRF from RT.

Question 29

Canadian, Whelan, trial included what kind of tumors? and did it show an OS or LC benefit?

Answer 29

showed hypofx had good results w/ no change in LC, DFS or OS or cosmesis. 1,234 women s/p lumpectomy if IDC and negative ALND to WBRT with 50/25fx or 42.5/16fx. no boost. >5cm tumors excluded, as well as >25cm separation. at 10yrs no difference in LC (6%), both good cosmesis (70%). no difference in OS or DFS. tmx was allowed. On long fu the G3 did worse in local control. But they did not use boost like the UK a/b

Question 30

UK START A AND B schemas? did they both allow boosts?

Answer 30

yes, both allowed boost. START A looked at pT1-3, N0-1 IDC to 50/25fx or 41.5/13fx or 39/13 fx. all treated over same time period of 5 weeks. SCV RT was allowed. LC 4-5%. On 10yr fu there was Less edema and telangiectasias in hypofx arm
START B looked at 50/25fx or 40/15 AH-different time periods. at 6yrs: LC same at 2-3%. unexpectedly better DM in AH arm and better DFS and OS. may disappear iwth longer f/u. This did not disappear on 10yr fu.

Question 31

what is the dose fx for ballon brachy for breast APBI?

Answer 31

3.4Gy BID x 5 days

3DCRT uses 3.85 Gy BID x 5 days

Question 32

what are the cautionary criteria for APBI per ASTRO?

Answer 32

Age between 50-59. Size between 2.1-3cm. close margins <=3cm. micrcoscopic multifocal.

Question 33

What is the suitable criteria for APBI per ASTRO?

Answer 33

> =60 yo. Size =2mm margins. ANY GRADE. no LVSI. ER+. unicentricity. IDC or other favorable histology. NO DCIS, NO EIC. LCIS OK. no neoadj tx, SLND or ALND allowed.

Question 34

what are the unsuitable criteria for APBI?

Answer 34

3cm, T3-4, +margins, extensive LVI, multicentric. etc.

Question 35

the MA 20 trial showed an improvement in DFS? did it show an improvement in OS? what was the randomization?

Answer 35

Randomized 1,800 women s/p BCS w/ adj chemo or endocrine tx to WB 50gy+/-bst vs WB+regional LN RT 45gy to scv, axilla, IM nodes.
10% were node neg. 85% had 1-3+LN. 5% had >4LN+. almost all got chemo adj and or adj endocrine. at 5 yrs, RNI improved LR DFS, distant DFS and overall DFS. trend to OS imrpovement only.

Question 36

NSABP B32 compared SLNDB + ALND to SLNB alone. what did it show?

Answer 36

doing SLNB in clinically negative axilla is ok. women with clinically negative axilla randomized and 99% LN were in levels I/II. mean number of LN removed was 2. morbidity of shoulder ROM was decreased in SLNB group. no difference in OS, DFS, RC between two arms.

Question 37

ACOSOG Z0011 trial with +SLN randomized to get ALND or no further surgery with WB tangents only showed what?

Answer 37

pT1-2 tumors with clinically negative axilla had 1-2+ SLN followed by ALND or not. at least 10 LN had to be removed at the ALND. median age was 55, mostly ER+ tumors. most women had only 1+LN. 27% pf women had additional positive LN on completion dissection. at 6 yrs there was no worse OS or DFS with just SLNB without ALND.

Question 38

The EBCTCG for chemotherapy showed what?

Answer 38

this metaanalysis regarding chemotherapy showed that all women receive a benefit from OS with 6 months of chemotherapy. with women <50 yrs getting the most benefit. RR of death is 38% in those younger than 50 compared to 20% in those over age 50, regardless of ER status, nodal status or other tumor charactersitics. N+ pts also benefit more than N- pts 11% vs 7%. Anthracycline chemo is better to CMF chemo with a 5yr OS benefit from 69% to 72%.

Question 39

The EBCTCG for RT showed what?

Answer 39

this metaanalysis showed that RT after BCS and mastectomy conferred a signficant absolute LC improvement of 20%, translating into a 5% absolute benefit in breast cancer mortality at 15yrs. RT did increase the risk of heart disease mortality by 1.27RR and lung cancer mortality 1.78RR. though these are all less than the improvement in BCSM.

Question 40

The EORTC boost trial showed what?

Answer 40

Stage I/II women after lumpectomy with negative margins got 50Gy +/- 16Gy bst. DCIS at the margin was allowed. some women with +margins got 10 vs 26Gy bst randomized.
16Gy bst decreased LF from 10 to 6%. the greatest benefit seen in those 60yrs. there was more severe fibrosis with bst. 4 vs 2%. no change in OS.

Question 41

Lyon boost trial showed what?

Answer 41

pts with lumpectomy, ALND got 50GY +/- 10Gy bst. at 5 yrs the boost decreased LF from 4.5 to 3.6%. same cosmesis, but slightly more telangiectasias.