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EBM

CRITICAL APPRAISAL
Lifetime Cigarette Smoking and Breast cancer
Prognosis in the After Breast cancer Pooling
Project

Disusun oleh :
Risa Apriliani
(1102013252)
Siti Aisyah Safira (1102013274)
Dosen Pembimbing :
Dr. Zwasta Pribadi Mahardika,M.Med.

FAKULTAS KEDOKTERAN
UNIVERSITAS YARSI
2015/2016

1.

SKENARIO:
Seorang wanita berumur 27 tahun datang ke poliklinik dengan keluhan terdapat
benjolan di payudara namun tanpa rasa nyeri serta didapatkan retraksi pada
papilla mammae. Saat anamnesis pasien adalah perokok aktif sejak 10 tahun yang
lalu, dan pasien mengatakan bahwa kira kira setiap harinya ia mengosumsi rokok
20-25 batang. Setelah dilakukan pemeriksaan lanjutan, pasien didiagnosis
karsinoma mammae.

2.

PERTANYAAN KLINIS:
Bagaimanakah angka harapan hidup wanita perokok aktif yang terkena kanker
payudara tersebut?

3.

KOMPONEN PICO:
Patient /Population/Problem : seorang wanita perokok aktif berumur 27 tahun
terkena kanker payudara
Intervention/ Indicator
:Comparison/Control
:Objective/Outcome
: angka harapan hidup wanita perokok aktif yang
terkena kanker payudara

4.

KATA KUNCI:
Lifetime cigarette smoking AND breast cancer AND prognosis

5.

PEMILIHAN SITUS:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906992/pdf/djt359.pdf

6.

LIMITED:
5 years

7.

HASIL PENCARIAN:
3 artikel

8.

ARTIKEL YANG DIPILIH:


Lifetime cigarette Smoking and Breast cancer Prognosis in the After Breast
cancer Pooling Project

APAKAH HASIL PENELITIAN TERSEBUT VALID?


A. Petunjuk Primer
1. Apakah terdapat sampel yang representatif, terdefinisi jelas, dan berada
pada kondisi yang sama dalam perjalanan penyakit?
Ya, karena di methods halaman 1 dan 2 dijelaskan berapa jumlah yang diikuti
dalam penelitian, dank arena kami tidak memberi batasan stadium, maka di
methods halaman 3 tercantum kata kata early stage dan stage 1.
Methods
Data were from three US cohorts in the After Breast Cancer Pooling
Project, with detailed information on smok- ing among 9975 breast cancer
survivors. Smoking was assessed an average of 2 years after diagnosis.
Delayed entry Cox proportional hazards models were used to examine the
relationships of smoking status, cigarettes per day, years of smoking, and
pack years with breast cancer prognosis. Endpoints included breast
cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and
overall mortality (n = 1803).
Our analytical sample included 9975 women aged 25 to 83 years at
diagnosis (mean = 59.2 years) of early-stage invasive primary breast
cancer between 1991 and 2006 (table 1). half of the sample had stage 1
disease, and a further 36.4% had stage 2 disease. more than half of the
tumors were moderately or well differentiated, and 61.5% were hormone
receptor positive. At the time of diagnosis, 23.9% or women were
premenopausal, and 71.8% were postmen- opausal. half of the sample
received chemotherapy, and 59.7% received radiation; 47.4% underwent
mastectomy, and 49.9% had breast-conserving surgery.
2. Apakah follow-up cukup lama dan lengkap?
Ya, karena pada results halaman 4 tertera follow up dilakukan sudah 11,1
tahun. Dan penelitian cukup lengkap karena dari yang mengikuti penelitian,
awalnya 9975 orang, dan pada akhirnya sisa 9755. Dimana disini menandakan
bahwa peserta yang diteliti masih lebih dari 80%. Data ini dapat dilihat pada
table 1 dan 2, dan akhir jumlah peserta pada table ke 3.
Results
Medianfollowuptimewas11.1yearsextendingthroughatleast2010,
andhealthendpointsincluded1727breastcancerrecurrences,1059
breastcancerdeaths,andatotalof1803deathsfromanycause.main
causesofdeathinthepooledcohortwerebreastcancer(58.6%),other
cancerdeaths(14.8%),andcardiovasculardiseases(10.1%).
B. Petunjuk sekunder
1. Apakah kriteria outcome yang digunakan obyektif dan tanpa bias?
Ya, objektif, karena kita menilai bagaimana angka kematian yang ada. Dan
tertera pada methods halaman 2 pada paragraph terakhir.
Methods
Mortality was assessed by periodic reviews of the Social

Security Death Index and the National Death Index for NhS and
WheL and additionally by Kaiser Permanente North California
electronic data sources for LACe. Cause of death was extracted
from National Death Index records, death certificates, or electronic medical records (Kaiser Permanente in LACe).
2. Bila ditemukan subgroup dengan prognosis yang beda, apakah dilakukan
adjustment untuk faktor-faktor prognostik yang penting?
Pada jurnal ini dilakukan adjustment untuk factor factor prognotik yang
penting antara lain : umur, stage cancer, status merokok, jumlah rokok per
hari, riwayat reproduksi, dll
Table 1. Demographic and clinical characteristics among breast cancer survivors who provided smoking
data (n = 9975)*
Characteristics
WHEL
LACE
NHS
All
Age at diagnosis, y, mean (SD)
51.3 (8.8)
59.3 (11.0)
64.8 (7.7)
59.2 (10.6)
Age at smoking questionnaire, y, mean (SD)
53.3 (9.0)
60.2 (11.0)
65.8 (7.8)
60.7 (10.5)
Age at questionnaire, y, range
2774
2782
4484
2784
Cancer stage, No. (%)
I
1184 (38.7) 1052 (46.6) 2752 (59.1) 4988 (50.0)
II
1391 (45.5) 952 (42.1)
1287 (27.6) 3630 (36.4)
III
482 (15.8)
254 (11.2)
415 (8.9)
1151 (11.5)
Unspecified
0
1 (0.0)
205 (4.4)
206 (2.1)
Tumor grade, No. (%)
Well differentiated
481 (15.7)
428 (19.0)
811 (17.4)
1720 (17.2)
Moderately differentiated
1231 (40.3) 941 (41.7)
1572 (33.7) 3744 (37.5)
Poorly differentiated
1092 (35.7) 676 (29.9)
1122 (24.2) 2895 (29.0)
Unspecified
253 (8.3)
214 (9.5)
1149 (24.7) 1616 (16.2)
Tumor hormone receptors, No. (%)
ER+/PR+
1894 (62.0) 1526 (67.6) 2718 (58.3) 6138 (61.5)
ER+/PR
366 (12.0)
318 (14.1)
669 (14.4)
1353 (13.6)
ER/PR+
126 (4.1)
41 (1.8)
120 (2.6)
287 (2.9)
ER/PR
606 (19.8)
350 (15.5)
648 (13.9)
1604 (16.1)
Unspecified
65 (2.1)
24 (1.1)
503 (10.8)
592 (5.9)
Cancer treatment, No. (%)
Radiation only
588 (19.2)
566 (25.1)
1652 (35.5) 2806 (28.1)
Chemotherapy only
841 (27.5)
435 (19.3)
625 (13.4)
1901 (19.1)
Radiation and chemotherapy
1288 (42.1) 856 (37.9)
1011 (21.7) 3155 (31.6)
Neither radiation nor chemotherapy
334 (10.9)
401 (17.8)
1062 (22.8) 1797 (18.0)
Unspecified
2 (0.1)
1 (0.0)
307 (6.6)
310 (3.1)
Surgery type, No. (%)
Mastectomy
1599 (52.3) 1115 (49.4) 2013 (43.2) 4727 (47.4)
Breast conserving
1457 (47.7) 1144 (50.6) 2376 (51.0) 4977 (49.9)
Unspecified
0
0
236 (5.1)
236 (2.4)
Diagnosis menopause status, No. (%)
Premenopausal
1555 (50.9) 513 (22.7)
217 (4.7)
2285 (23.9)
Postmenopausal
1414 (46.3) 1436 (6.6)
4314 (92.6) 7164 (71.8)
Equivocal
88 (2.9)
310 (13.7)
128 (2.7)
* ER = estrogen receptor; LACE = Life After Cancer Study; NHS = Nurses Health Study; PR =
progesterone receptor; WHEL = Womens Healthy Eating and Living Study; SD = standard deviation.

Table 2. Smoking history among three cohorts of US breast cancer survivors (n =


9975)*
Smoking history

WHEL No. (%)

LACE No. (%)

NHS No. (%) All No. (%)

Never

1643 (53.8)

1195 (52.9)

1974 (42.4)

4812 (48.2)

Current

138 (4.5)

173 (7.7)

399 (8.6)

710 (7.1)

Former

1276 (41.7)

891 (39.4)

2272 (48.8)

4439 (44.5)

Unspecified

14 (0.3)

14 (0.1)

<5

32 (23.2)

22 (12.7)

38 (9.5)

92 (13.0)

514

62 (44.9)

83 (48.0)

125 (31.3)

270 (38.0)

1524

32 (23.2)

55 (31.8)

155 (38.9)

242 (34.1)

25

12 (8.7)

9 (5.2)

60 (15.0)

81 (11.4)

Unspecified

4 (2.3)

21 (5.3)

25 (3.5)

<5

350 (27.5)

155 (17.4)

342 (15.1)

847 (19.1)

514

388 (30.4)

283 (31.8)

736 (32.4)

1407 (31.7)

1524

340 (26.7)

293 (32.9)

743 (32.7)

1376 (31.0)

25

189 (14.8)

132 (14.8)

376 (16.6)

697 (15.7)

Unspecified

9 (0.7)

28 (3.1)

75 (2.4)

112 (2.5)

<10

13 (9.4)

4 (2.3)

3 (0.8)

20 (2.8)

1019

24 (17.4)

11 (6.4)

4 (1.0)

39 (5.5)

2029

46 (33.3)

38 (22.0)

8 (2.0)

92 (13.0)

30

55 (39.9)

118 (68.2)

377 (94.5)

550 (77.5)

Unspecified

2 (1.2)

7 (1.8)

9 (1.3)

<10

572 (44.8)

208 (23.3)

413 (18.2)

1193 (26.9)

1019

335 (26.3)

234 (26.3)

525 (23.1)

1094 (24.7)

Smoking status

Cigarettes/day
Current smokers

Former smokers

Years of smoking
Current smokers

Former smokers

2029

237 (18.6)

207 (23.2)

486 (21.4)

930 (21.0)

30

125 (9.8)

234 (25.1)

807 (35.5)

1156 (26.0)

Unspecified

7 (0.6)

18 (2.0)

41 (1.8)

66 (1.5)

1644 (53.8)

1197 (53.0)

1974 (42.4)

4815 (48.3)

0.110

775 (25.4)

467 (20.7)

803 (17.2)

2045 (20.5)

10.119.9

245 (8.0)

167 (7.4)

457 (9.8)

869 (8.7)

20.034.9

199 (6.5)

201 (8.9)

545 (11.7)

945 (9.5)

35

179 (5.9)

188 (8.3)

796 (17.1)

1163 (11.7)

Pack-years

Unspecified
15 (0.5)
39 (1.7)
84 (1.8)
138 (1.4)
* LACE = Life After Cancer Study; NHS = Nurses Health Study; WHEL = Womens
Healthy Eating and Living Study;
APA HASILNYA?
1. Bagaimana gambaran outcome menurut waktu?
dapat dilihat dari kurva, bahwa bagi penderita dengan kebiasaan merokok aktif
memiliki angka harapan hidup lebih rendah daripada yang tidak merokok.

2. Seberapa tepat perkiraan prognosis?


Tepat, karena disini didapatkan HR 2.17 95% CI (1,85-2,54). Dan disini dapat
dilihat angkat kematian akan lebih meningkat pada perokok aktif daripada
tidak merokok.
Table 3. Adjusted Cox models* examining the associations of smoking with breast cancer
recurrence and mortality in a pooled cohort of US breast cancer survivors (n = 9755)
Breast cancer recurrence
Smoking status

No.

Event

HR (95% CI)

Never smokers

4812

824

Referent

<20 pack-years

2744

453

0.98 (0.87 to 1.11)

2034.9 packyears

808

156

35 pack-years

785

Current
smokers

710

Breast cancer mortality


P

Event

HR (95% CI)

499

Referent

.78

259

0.99 (0.85 to 1.15)

1.22 (1.01 to 1.48)

.04

93

155

1.37 (1.13 to 1.66)

.001

139

1.41 (1.16 to 1.71)

<.001

All-cause mortality
P

Event

HR (95% CI)

780

Referent

.88

410

0.97 (0.86 to
1.09)

.58

1.14 (0.91 to 1.43)

.26

177

1.26 (1.07 to
1.48)

.01

111

1.54 (1.24 to 1.91)

<.001

227

1.68 (1.44 to
1.96)

<.001

97

1.61 (1.28 to 2.03)

<.001

209

2.17 (1.85 to
2.54)

<.001

Former smokers

P trend

<.001

<.001

<.001

* Hazard ratios (HRs) were from delayed-entry Cox regression models with study as a stratification
variable and adjusted for age at diagnosis, cancer stage, tumor grade, race/ethnicity, education, and
obesity. CI = confidence interval; SD = standard deviation.
P values (two-sided) were from the Wald test within Cox proportional hazards regression.
Current smokers had smoked for a mean of 39 (standard deviation = 25) pack-years.
Compared with never smokers, former smokers with low lifetime smoking
exposure (<20 pack-years) had no increased risk of any outcome. In former
smokers with heavier exposures, there was a doseresponse relationship
between increasing lifetime smoking exposure and the risk for all-cause
mortality (P trend < .0001) and breast cancer mortality (P trend < .0001).
Specifically, compared with never smokers, former smokers with 20 to 34.9
pack-years of exposure had a 22% increased risk of breast cancer recurrence
(HR = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased
risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former
smokers with 35 or more pack-years of exposure, the probability of breast
cancer recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66),
breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91),
and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96).
Current smokers in this study had a mean exposure of 39 pack years.
Compared with nonsmokers, the probability of a breast cancer recurrence in
smokers was 41% higher (HR = 1.41; 95% CI = 1.16 to 1.71), breast cancer
mortality was 60% higher (HR = 1.61; 95% CI = 1.28 to 2.03), and there was
double the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54).
There appeared to be little difference in risk for any outcome between current
smokers and former smokers with 35 or more pack-years of exposure.

APAKAH HASIL PENELITIAN INI DAPAT DIAPLIKASIKAN?


1. Apakah pasien dalam penelitian tersebut serupa dengan pasien saya?
Ya, karena pasien di scenario berumur 27 tahun, sedangkan di jurnal penelitian
ini dilakukan pada range umur 25-83 tahun, lalu di scenario kami mengatakan
kira kira 20-25 batang sehari, di table 2 didapatkan kriteria tersebut. Lalu di
scenario kami mengatakan bahwa pasien telah merokok kurang lebih 10 tahun,
dan di table 2 juga ada kriteria tersebut.
2. Apakah hasil tersebut membantu memilih atau menghindari terapi
tertentu?
Ya, pada jurnal ini tidak hanya menjelaskan tentang kebiasaan merokok pada
penderita kanker payudara saja, tetapi bisa untuk semua penyakit dan
didapatkan bahwa perokok aktif meningkatakan angkat kematian pada seluruh
penyakit. Kanker sangat sulit disembuhkan, sehingga kita dapat memberikan
edukasi kepada pasien untuk menjaga pola hidupnya terutama untuk
menghindari kebiasaan merokok agar keberlangsungan hidupnya dapat lebih
baik.
3. Apakah hasilnya membantu dalam memberikan konseling kepada pasien
saya?
Ya, menurut jurnal ini didapatkan angkat kehidupan pada penderita kanker
akan menurut jika ia perokok aktif, maka dari itu jika seorang pasien yang
datang adalah seorang perokok aktif maka akan diberi konseling untuk
berhenti merokok, lalu jika pasien datang bukan seorang perokok maka
diberikan konseling untuk tidak merokok, karena hal tersebut dapat
berdampak tidak baik.