EVIDENCE BASED MEDICINE

Relationship of Body Mass Index with Prognosis in Breast Cancer

Patients Treated with Adjuvant Radiotheraphy and
Chemotheraphy
Pengarang Jurnal : Yasemin Benderli Cihan

Dosen pembimbing : dr. Ida Ratna Nurhidayati Sp.S

Disusun Oleh :
Annisa Rahmadhania : 1102013038
Diana yunus : 1102013083
 SKENARIO
Seorang wanita berumur 52 tahun, ibu rumah tangga, mempunyai 2 orang anak usia
20 tahun dan 18 tahun datang ke rumah sakit karena merasakan adanya benjolan pada
payudara sebelah kanan yang semakin lama semakin membesar sejak 3 bulan terakhir dan
tidak terasa nyeri. Ibu pasien 3 tahun lalu meninggal karena kanker payudara.
Pada pemeriksaan fisik didapatkan keadaan umum baik, vital sign dalam keadaan
normal, BMI 35,5 kg/m² (N:25-29,9 kg/m²). Hasil pemeriksaan inspeksi payudara kanan
dan kiri tampak simetris, tidak ditemukan ulkus dan retraksi pada papilla mammae, tidak
tampak adanya skin rash ataupun peau d’orange pada kedua payudara. pada pemeriksaan
palpasi ditemukan adanya benjolan di region mammae dextra kuadran lateral atas ukuran
2x2x1 cm3, permukaan licin, konsistensi kenyal, terfiksisir dan tidak ada nipple discharge.
Pada saluran getah bening di ketiak ditemukan adanya 1 benjoliopsisan ukuran 1x1x1
cm3. Dokter mencurigai pasien terkena kanker payudara dan menyarankan melakukan
pemeriksaan mammografi dan USG untuk mendeteksi kanker payudara pada tahap awal
dan menunjukkan lesi yang tidak bisa di deteksi dengan pemeriksaan klinis. Biopsi insisi
memastikan pasien menderita kanker payudara stadium II kemudian menjalani operasi
mastektomi radikal dilanjutkan dengan kemoterapi dan radioterapi. Pasien menanyakan
kemungkinan penyakitnya, apakah BMI yang tinggi dapat mempengaruhi lama
penyembuhan penyakitnya?
Pertanyaan (Foreground Question)?

 Apakah Body Mass Index (BMI) mempengaruhi prognosis pada pasien kanker
payudara stadium II?

PICO
 Population : wanita dengan karsinoma payudara stadium II
 Intervention : BMI > 30 kg/m²
 Comparison : BMI < 30 kg/m²
 Outcome : BMI > 30 kg/m² menurunkan angka survival rate kanker payudara
stadium II
PENCARIAN BUKTI ILMIAH

 Alamat website : http://www.ncbi.nlm.nih.gov/pubmed/

 Kata kunci : women AND breast cancer AND prognosis AND
body mass index
 Limitasi : Januari 2011- Maret 2016
 Hasil pencarian : 69

 Dipilih artikel berjudul

Relationship of Body Mass Index with Prognosis in Breast Cancer Patients Treated
with Adjuvant Radiotheraphy and Chemotheraphy
 Latar Belakang

Kami meninjau dengan metode retrospektif. 456 pasien yang di diagnosis kanker
payudara di Departemen Radiasi Onkologi dari Kayseri teaching hospital antara tahun
2005 dan 2013. Kami menginvestigasi hubungan dari indeks massa tubuh dengan
prognosis dan faktor prognosis lainnya.
Penelitian ini melibatkan 456 pasien (447 wanita dan 9 pria). Usia rata-rata pada
presentase adalah 55,6 tahun. Dari kasus, 96,9% dimodifikasi dengan mastektomi
radikal, dan 95% mendapatkan kemoterapi, sedangkan 82,4% mendapatkan
radioterapi dan 60% diberi terapi hormon. Indeks massa tubuh >25mg/kg2 dalam 343
kasus. 5 dan 10 tahun secara keseluruhan angka harapan hidup adalah masing-masing
65% dan 49%.
 Penelitian

 Waktu : tahun 2005 dan 2013

 Tempat : Department of Radiation Oncology, Kayseri Education and
Research Hospital, Kayseri, Turkey
 Design :
 Populasi : 456 pasien (447 wanita dan 9 pria)
 Sampel
456 pasien (447 wanita dan 9 pria)
Usia rata-rata 55,6 tahun

 96,6,% mastektomi total

 95% kemoterapi
 82,4% radioterapi
 60% terapi hormonal

IMT > 25 mg/k dalam 343 kasus

Dengan harapan hidup 65% sampai 49%

I. APAKAH HASILNYA VALID
1. Apakah terdapat sampel yang representative dan didefinisikan secara jelas pada kondisi
yang sama/ similar point dalam perjalanan penyakit/ course of the disease?
 Ya, jurnal ini mengambil sampel dengan cara meninjau dengan metode retrospektif pada
456 pasien yang di diagnosis kanker payudara di Departemen Radiasi dan Onkologi dari
Kayseri teaching hospital antara tahun 2005 dan 2013.

We retrospectively reviewed operated breast cancer patients who were followed in Radiation
Oncology department of Kayseri Teaching Hospital between 2005 and 2013. Patients with
missing data and those lost in follow- up were excluded from analysis. The study was planned
in accordance to local ethics regulations and Helsinki Declaration. We reviewed age, gender,
menopausal status, family history of breast cancer, height, weight, BMI, tumor localization,
tumor stage, surgery type, histopathological findings, data regarding chemotherapy and
radiotherapy, and survival times. In the histopathological diagnosis, tumor type, tumor
localization, tumor diameter, lymphatic metastasis, number of lymph nodes excised, number
of lymph nodes with metastatic infiltration, level of estrogen and progesterone receptors,
cerb-B2 status, grade, and lymphovascular and perineural invasion status were recorded.
2. Apakah follow up lengkap dan cukup lama/ sufficiently long and complete?
 Subjek penelitian ini di follow up cukup lama yaitu dijadwalkan tiap 3 bulan dalam satu tahun;
dua kali tiap tahun sampe tahun ke lima; dan setiap tahun
We retrospectively reviewed operated breast cancer patients who were followed in Radiation
Oncology department of Kayseri Teaching Hospital between 2005 and 2013. Patients with missing
data and those lost in follow- up were excluded from analysis.
Follow-up visits were scheduled by 3-months interval within first year; biannually until end of year
5; and annually thereafter. Complete blood count, biochemical parameters, and Ca 15-3 and CEA
levels were measured biannually, while chest radiographs, mammography, abdominal sonography
and bone scintigrapy were obtained annually.

3. Apakah digunakan kriteria outcome yang objektif dan tidak berbias?

 Kriteria outcome ini bersifat objektif karena membandingkan 2 hal antara yang memiliki indeks
massa tubuh normal dan tidak normal dan faktor risiko lainnya terhadp kejadian kanker payudara.
We retrospectively reviewed operated breast cancer patients who were followed in Radiation
Oncology department of Kayseri Teaching Hospital between 2005 and 2013. Patients with missing
data and those lost in follow- up were excluded from analysis. The study was planned in accordance
to local ethics regulations and Helsinki Declaration. We reviewed age, gender, menopausal status,
4. Bila ditemukan subgroup dengan prognosis yang berbeda, apakah dilakukan adjusment untuk faktor – faktor
prognostik yang penting?
 Pada jurnal ini dilakukan adjusment untuk faktor- faktor prognostik lain yaitu:
Demografik, jenis kelamin, usia, status menopuse, riwayat keluarga yang terkena kanker payudara, lokasi tumor, tipe
histologi, ukuran tumor, status limfonodus, status ER, status PR, HER2, keterkaitan perinodal, invasi limpovaskular,
operasi, kemoterapi, radioterapi, terapi hormon.
Indeks massa tubuh (berat badan rendah:<18,5kg/m2 ; berat badan normal:18,5-24,9 ; obesitas grade 1: 25,0-29,9 kg/m2 ;
obesitas grade 2: 30,0-39,9 kg/m2 ; obesitas grade 3:>40 kg/m2)
 II. APAKAH HASIL PENELITIAN INI PENTING
1. Bagaimana gambaran outcome
menurut waktu?
Seberapa tepat perkiraan prognosis?
 Hasil yang didapatkan sesuai dengan perkiraan bahwa indeks massa tubuh memiliki hubungan
yang terkait secara signifikan terhadap prognosis kanker payudara.
Table 1 presents mean OS and PFS rates and factors affecting OS and PFS. Mean OS was
125.8 months and 5- and 10-years OS rates were calculated as 77% and 58%, respectively.
Factors associated with OS were found as T size (p=0.004), lymph node metastasis (p=0.003) and
BMI (p=0.008). When OS was assessed according to BMI, it was found that mean OS was 95.2
months in cases with BMI<18.5 kg/m2, 168.8 months in cases with BMI of 18.5-24.9 kg/m2, and
<89 months in cases with BMI ≥25.0 kg/m2. It was found that OS was worse in both
underweight and obese patients (Figure 1). Mean PFS was 108.8 months and 5- and 10-years
PFS rates were 65% and 49%. Univariate analysis of factors affecting PFS was
Table 2 and 3 present results of univariate and multivariate analysis for OS and PFS
according to risk factors. In univariate analysis, factors including height (p=0.048), stage
(p=0.046), tumor diameter (p=0.001), lymph node metastasis (p=0.006) and BMI (p=0.030) were
found to be significantly associated with OS. In multivariate analysis, stage (p=0.032; OR: 3.8;
95% CI: 1.1-13), tumor diameter (p<0.000; OR: 0.0; 95% CI: 0.0-0.3), lymph node metastasis
(p=0.005; OR: 0.0; 95% CI: 0.0-0.5) and BMI (p=0.027; OR: 0.02; 95% CI: 0.0-0.8) remained
to be significantly associated with OS. In univariate and multivariate analysis, perinodal
involvement was the only factor that was significantly associated with PFS (p=0.018).
III. APAKAH HASIL PENELITIAN INI DAPAT DIAPLIKASIKAN
1. Apakah pasien dalam penelitian tersebut serupa dengan pasien saya?
 Ya, karena pada jurnal ini membandingkan prognosis kanker payudara
pada seseorang yang memiliki indeks massa tubuh dalam kategori
underweight, normal dan obesitas
2. Apakah hasil penelitian membantu dalam keputusan pemilihan terapi?
 Ya, pada jurnal ini tidak hanya menjelaskan tentang indeks massa tubuh, tetapi juga
menjelaskan hubungan kanker payudara dengan status menopuse, tipe histologi,
kemoterapi dan terapi hormon

In terms of breast cancer, it was shown that low body weight increases risk during
premenopausal period, while increased body weight increases risk during postmenopausal
period. As a result, investigators began to evaluate prognostic value of obesity in breast
cancer,
In our study, significant correlations were detected between BMI and menopausal status,
histological type, chemotherapy and hormone therapy. It has been thought that many
metabolic and hormonal pathways are involved in the relationship between obesity and
prognosis.
that hormone therapy was less effective in women with higher BMI. There are several
randomized studies comparing AIs and tamoxifen in adjuvant treatment of breast cancer
effects of BMI on relative effectiveness of AI and tamoxifen were reported in four of these
studies (ATAC, BIG 1-98 and TEAM in the postmenopausal setting and ABCSG-12 in the
premenopausal setting).
In the study by Ladoire et al., it was reported that obesity remained to be associated with
poorer baseline tumor characteristics but had no effect on the prognosis when modern
adjuvant chemotherapy was delivered at appropriate doses (Ladoire et al., 2014).
3. Apakah penelitian berguna untuk konseling pada penderita dan keluarganya?
 Ya, menurut jurnal ini ada hubungan antara indeks massa tubuh dengan prognosis kanker
payudara.

In conclusion, in our study, it was found that overall survival was shorter in patients with
BMI<18.5 kg/m2 or >25.0 kg/m2 when compared to other patient groups. In addition, it was
also found that progression-free survival was shorter but the difference didn’t reach statistical
significance. We think that this finding could be due to small sample size. These findings should
be further tested in comprehensive studies.
In our study, 343 of 456 patients were in obesity group with a BMI >25 kg/m2. It was found
that OS was significantly higher in the group with normal BMI when compared to those in
the underweight and obese patient groups. It was found that the factors significantly
associated with OS were stage, tumor diameter, lymph node metastasis and BMI.
 Kesimpulan

Dalam penelitian ini, dapat dilihat bahwa waktu overall survival lebih pendek pada
pasien dengan berat badan rendah dan obesitas dibandingkan dengan berat badan
normal