Hartmann O, et al DNA methylation markers predict outcome in
node-positive, estrogen receptor-positive breast cancer with adjuvant
anthracycline-based chemotherapy. Clin Cancer Res. 2009 Jan
1;15(1):315-23.
Hartmann and colleagues analyzed DNA methylation in regulatory regions
of PITX2 and 60 additional candidate genes using a microarray
platform, in 241 breast cancer specimens. The tumours were lymph
node-positive, estrogen receptor-positive and HER-2-negative. All
patients were treated with anthracycline-based chemotherapy.
Using Cox regression analysis, the authors assessed the predictive
power of the individual marker and observed that DNA methylation of
PITX2 and 14 other genes was correlated with clinical outcome. A
four-marker panel including PITX2, BMP4, FGF4, and C20orf55 was found
to improve outcome prediction compared with PITX2 alone. This study
provides further evidence that a well-defined panel of DNA methylation
markers is a useful prognostic indicator in human breast cancer.
Gunter MJ, et al. Insulin, Insulin-Like Growth Factor-I, and Risk of
Breast Cancer in Postmenopausal Women. J Natl Cancer Inst. 2008 Dec
30. [Epub ahead of print]
Gunter and colleagues evaluated the fasting serum levels of insulin,
glucose, total IGF-I, free IGF-I, insulin-like growth factor binding
protein-3, and oestradiol at study entry from 835 incident breast
cancer case subjects and from a sub-group of 816 randomly chosen from
the Women's Health Initiative Observational Study (WHI-OS): a
prospective cohort of 93 676 postmenopausal women. Multivariable Cox
proportional hazards models were used to estimate associations between
levels of the serologic factors and baseline characteristics and the
risk of breast cancer. All statistical tests were two-sided. The
authors observed that insulin levels were positively associated with
the risk of breast cancer (hazard ratio [HR] for highest vs lowest
quartile of insulin level = 1.46, 95% confidence interval [CI] = 1.00
to 2.13, P(trend) = .02); however, the association with insulin level
varied by hormone therapy (HT) use (P(interaction) = .01). In a model
that controlled for multiple breast cancer risk factors including
estradiol, insulin level was associated with breast cancer only among
nonusers of HRT (HR for highest versus lowest quartile of insulin
level = 2.40, 95% CI = 1.30 to 4.41, P(trend) < .001). Obesity (BMI
>/=30 kg/m(2)) was also associated with the risk of breast cancer
among nonusers of HRT (HR for BMI >/=30 kg/m(2) vs 18.5 to <25 kg/m(2)
= 2.12, 95% CI = 1.26 to 3.58, P(trend) = .003). These results suggest
that hyperinsulinemia is an independent risk factor for breast cancer
and may have a substantial role in explaining the obesity-breast
cancer relationship. Leptin is another factor that is thought to be
involved in mediating the role of obesity in increasing breast cancer
risk.
Classe JM et al. Sentinel Lymph Node Biopsy After Neoadjuvant
Chemotherapy for Advanced Breast Cancer: Results of Ganglion
Sentinelle et Chimiotherapie Neoadjuvante, a French Prospective
Multicentric Study. J Clin Oncol. 2008 Dec 29. [Epub ahead of print]
Classe JM and colleagues investigated the detection rate, the
false-negative rate, and the accuracy of sentinel lymph node (SLN)
detection after neoadjuvant chemotherapy (NC) for advanced breast
cancer. 195 patients enrolled from 12 institutions were recruited to a
prospective multi-centre study. The authors observed that the
detection rate was 90% (176 of 195 patients), and the false-negative
rate was 11.5% (6 of 52 patients). Patients without axillary palpable
nodes (N0) before NAC had a better detection rate compared with
patients with axillary suspicious nodes (N1, 94.6% v 81.5%; P =
0.008). The false-negative rate was not correlated with clinical nodal
status before NC (9.4% v 15%; P =0.66). This study confirms the
feasibility of SLN biopsy after NC in locally-advanced operable breast
cancer. The detection rate, false-negative rate, and accuracy are
similar to those reported for early breast cancer without NC.
Kwan ML, et al. Dietary Patterns and Breast Cancer Recurrence and
Survival Among Women With Early-Stage Breast Cancer. J Clin Oncol.
2008 Dec 29. [Epub ahead of print]
In a study of 1,901 Life After Cancer Epidemiology Study
participants diagnosed with early-stage breast cancer between 1997
and 2000 (recruited primarily from the Kaiser Permanente Northern
California Cancer Registry) Kwan ML et al investigated dietary
patterns and overall survival and breast cancer outcome.
Diet was assessed at cohort entry using a food frequency
questionnaire. Two dietary patterns were identified: prudent (high
intakes of fruits, vegetables, whole grains, and poultry) and
Western (high intakes of red and processed meats and refined
grains). Two hundred sixty-eight breast cancer recurrences and 226
all-cause deaths (128 attributable to breast cancer) were recorded.
Using Cox proportional hazards models, the authors observed that
increasing adherence to a prudent dietary pattern was associated
with a statistically significant decreasing risk of overall death (P
trend = .02; HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90)
and death from non-breast cancer causes (P trend = .003; HR for
highest quartile = 0.35; 95% CI, 0.17 to 0.73). In contrast,
increasing consumption of a Western dietary pattern was related to
an increasing risk of overall death (P trend = .05) and death from
non-breast cancer causes (P = .02). Neither dietary pattern was
associated with risk of breast cancer recurrence or death from
breast cancer.
This study shows that although diet does not influence breast cancer
outcome, however women diagnosed with early-stage breast cancer
might improve overall prognosis and survival by adopting healthier
dietary patterns.
Holli K et al. Radiotherapy After Segmental Resection of Breast
Cancer With Favorable Prognostic Features: 12-Year Follow-Up Results
of a Randomized Trial. J Clin Oncol. 2008 Dec 29. [Epub ahead of
print]
Holli K and colleagues investigated the benefits of radiotherapy (RT)
in 264 women older than 40 years who were treated by breast
resection with >/= 1 cm of tumor-free margin and axillary nodal
dissection and were randomly assigned to receive or not to receive
RT
(the cumulative dose was 50 Gy) after surgery. All patients had
T1N0M0 ER+ve tumours.
Furthermore, the tumours were well to moderately differentiated and
unifocal, and of low cell proliferation rate (ie, S phase fraction
</= 7% or nuclear Ki-67 expression < 10%) and had to lack an
extensive intraductal component. After a median follow-up time of
12.1 years, the authors observed 16 (11.6%) and 34 (27.2%) local
recurrences in the RT and the control arms, respectively (P =
.0013). Time to local recurrence was longer in the RT arm (hazard
ratio [HR], 0.36; 95% CI, 0.20 to 0.65; P = .00071). Twenty-one
patients assigned to radiotherapy and 26 assigned to control died
during the follow-up. There were no differences in overall survival
time (HR, 0.63; 95% CI, 0.35 to 1.12; P = .11), distant disease-free
survival (P = .94), or breast cancer-specific survival (P = .56)
between the RT and control groups.
This study provides further evidence that RT reduces the incidence
of ipsilateral breast recurrence, even among women with good
prognosis small-size breast tumours excised with a minimal surgical
margin of 1cm. However, RT did not significantly improve survival.
Borley AC , et al. Anti-oestrogens but not oestrogen deprivation
promote cellular invasion in intercellular adhesion-deficient breast
cancer cells. Breast Cancer Res. 2008 Dec 4;10(6):R103. [Epub ahead
of print]
Borley and colleagues investigated the effects of tamoxifen and
fulvestrant treatment on invasive signalling and compared this with
the direct effects of oestrogen deprivation using
endocrine-sensitive MCF-7 cells, in the presence or absence of
functional E-cadherin.
The authors studied the effect of oestrogen and 4-hydroxy-tamoxifen
on the invasive capacity (as determined by Matrigel invasion assays)
of these cells. Western blotting using phospho-specific antibodies
was performed to ascertain changes in invasive signalling in
response to the two anti-oestrogens versus oestradiol treatment and
withdrawal. The authors observed that tamoxifen was able to promote
an invasive phenotype in ER-positive breast cancer cells in the
absence of functional E-cadherin. This suggests a role for Src
kinase and associated pro-invasive genes in this process. The study
showed that although this adverse effect was also apparent for the
steroidal anti-oestrogen fulvestrant, it was absent during oestrogen
withdrawal. These findings are also consistent with a recent study
showing that the absence of E-cadherin predicts tamoxifen resistance
in patients with ER+ve breast cancer. Therefore it may be prudent to
consider the use of aromatase inhibitors in preference to
anti-oestrogens in patients with ER+ve and E-cadherin-ve breast
cancer.
|
|
