2260

The Effects of Radiation Therapy on Quality of Life of

Women with Breast Carcinoma
Results of a Randomized Trial

Timothy J. Whelan, B.M., B.Ch., M.Sc.1,2,3
Mark Levine, M.D.2,3
Jim Julian, M.Math. 3
Peter Kirkbride, M.D.4,5
Peter Skingley3
for the Ontario Clinical Oncology
Group
1
Cancer Care Ontario, Hamilton Regional Cancer
Centre, Hamilton, Ontario, Canada.
2
Department of Medicine, McMaster University,
Hamilton, Ontario, Canada.
3 421 to no further treatment. The mean change in quality of life from baseline to 2
Department of Clinical Epidemiology and Biosta-
tistics, McMaster University, Hamilton, Ontario,
Canada.
4 radiation therapy increased the proportion of patients who were troubled by
Ontario Cancer Institute, Princess Margaret Hos-
pital, Toronto, Ontario, Canada.
5
University of Toronto, Toronto, Ontario, Canada.
Presented at the 39th Annual Meeting of the Amer-
ican Society for Therapeutic Radiology and Oncol-
ogy, Orlando, Florida, October 19 –23, 1997.
Other members of the Ontario Clinical Oncology
Group are as follows: P. B. McCulloch, Cancer Care
Ontario (CCO) Hamilton Regional Cancer Centre,
Hamilton; M. Lipa, Toronto Hospital, Toronto; L. J.
Mahoney, St. Michael’s Hospital, Toronto; B. D.
Nair, CCO Ottawa Regional Cancer Centre, Ottawa;
F. Perera, CCO London Regional Cancer Centre,
London; C. S. Wong, Ontario Cancer Institute, Prin-
cess Margaret Hospital, Toronto; Ontario, Canada.
This study was performed at the Hamilton Civic
Hospitals Research Centre, McMaster University,
Hamilton, Ontario, Canada.
Address for reprints: Timothy J. Whelan, B.M.,
B.Ch., M.Sc., Hamilton Regional Cancer Centre,
699 Concession Street, Hamilton ON L8V 5C2,
Canada.
Received July 14, 1999; revision received Decem-
ber 23, 1999; accepted January 21, 2000.
BACKGROUND. The purpose of this study was to evaluate the effect of breast
irradiation on quality of life, including cosmetic outcome, for patients enrolled in
a clinical trial.
METHODS. Between 1984 and 1989, a randomized trial was conducted in Ontario,
Canada, in which women with lymph node negative breast carcinoma who had
undergone lumpectomy and axillary lymph node dissection were randomized to
either breast irradiation or no further treatment. A modified version of the Breast
Cancer Chemotherapy Questionnaire (BCQ) was administered to women at base-
line, 1 month (4 weeks), and 2 months (8 weeks) after randomization. Irritation of
the skin of the breast, breast pain, and appearance of the breast to the patient were
also assessed every 3 months for the first 2 years of the study.
RESULTS. Of 837 patients, 416 were randomly allocated to radiation therapy and
months was ⫺0.05 for the radiation group and ⫹0.30 for the control group. The
difference between groups was statistically significant (P ⫽ 0.0001). Longer term
irritation of the skin of the breast and breast pain. Radiation therapy did not
increase the proportion of patients at 2 years who were troubled by the appearance
of the treated breast; 4.8% in irradiated and nonirradiated patients (P ⫽ 0.62).
CONCLUSIONS. Breast irradiation therapy had an effect on quality of life during
treatment. After treatment, irradiated patients reported increased breast symp-
toms compared with controls. However, no difference was detected between
groups at 2 years in the rates of skin irritation, breast pain, and being upset by the
appearance of the breast. Cancer 2000;88:2260 – 6.
© 2000 American Cancer Society.
KEYWORDS: randomized trial, breast neoplasm, radiation therapy, quality of life.
B reast-conserving surgery is now commonly used in the treatment
of women with early stage breast carcinoma.1,2 Five published
randomized trials have demonstrated that breast irradiation after
surgery substantially reduces the risk of recurrence of carcinoma in
the breast.3–7 In the Ontario trial, women with lymph node negative
breast carcinoma treated by lumpectomy and axillary lymph node
dissection were randomized to breast irradiation or no further treat-
ment after surgery.5 At a median follow-up of 7.6 years, the risk of
local recurrence was reduced from 35% in nonirradiated patients to
11% in irradiated patients. No difference was detected in overall
survival. Based on the results of these and other clinical trials, breast
irradiation is commonly offered to women after lumpectomy to pre-
vent local recurrence and the need for mastectomy.

© 2000 American Cancer Society


Breast irradiation usually is given daily, except
weekends, for 3– 6.5 weeks. It is associated with rec-
ognized short term side effects (within 3 months of
completion of treatment) of fatigue and skin ery-
thema, and more medium and long term side effects
(3 months to 3 years after treatment) of breast edema,
pain, fibrosis, and telangiectasia.8 Many of the long
term side effects are thought to impinge on cosmetic
outcome.
Recently in health care, there has been increased
recognition of the need to measure the effects of treat-
ment on a patient’s quality of life. Quality of life refers
to the wide variety of subjective experiences (such as
symptoms, physical function, emotional function, and
social function) that are related to health.9 In clinical
decision making, the benefits of radiation therapy in
preventing local recurrence must be weighed against
the impact of treatment on a patient’s quality of life.
Previous studies of patients treated by mastec-
tomy have suggested that the addition of postopera-
tive radiotherapy was associated with a higher inci-
dence of psychologic morbidity, such as depression
and anxiety.10,11 Studies of breast-conserving therapy
(lumpectomy plus breast irradiation) also have sug-
gested that this treatment as compared with mastec-
tomy or lumpectomy alone may be associated with an
increase in affective symptoms.12,13 Other studies have
not shown an effect of postoperative radiation therapy
on psychologic distress but have suggested significant
effects on physical symptoms, in particular, fa-
tigue.14 –16 Many of these studies have involved small
numbers of patients, nonrandomized comparisons
and multiple end points increasing the possibility of
falsely attributing observed differences to the effect of
treatment. The purpose of this study was to evaluate
the effect of breast irradiation after lumpectomy on
quality of life and cosmetic outcome in women with
axillary lymph node negative breast carcinoma in a
randomized controlled trial.
METHODS
Details of the study design have been published pre-
viously17 but are outlined briefly. From April 1984
through to February 1989, consecutive patients with
breast carcinoma treated by lumpectomy and axillary
lymph node dissection who had been referred to the
Princess Margaret Hospital in Toronto or the Ontario
Cancer Treatment and Research Foundation Regional
Cancer Centres in Hamilton, London, Ottawa, Wind-
sor and Thunder Bay, Ontario, Canada were ap-
proached for study entry. Eligibility criteria required
that the tumor be ⱕ 4 cm in diameter, that local
excision was microscopically complete, and that there
was no evidence of histologic involvement of axillary
Quality of Life with Breast Irradiation/Whelan et al. 2261
lymph nodes. Informed consent was obtained from
eligible patients before randomization. Eligible pa-
tients who agreed to participate were randomized to
receive local breast irradiation or no further treat-
ment.
Patients assigned to radiation therapy received a
dose of 40 gray (Gy), given by cobalt-60 over a period
of 3 weeks with 16 daily fractions to the entire breast.
Subsequently, a boost was given to the primary site
using a direct field to give a dose of 12.5 Gy in 5 daily
fractions. The breast was irradiated by a means of a
parallel opposed pair of tangential, partially wedged
fields. Bolus material was not used. Radiation therapy
was delivered daily, Monday to Friday. Patients did
not receive postoperative adjuvant systemic therapy.
Quality of Life
Acute phase (0 –2 months after randomization)
A modified version of the Breast Cancer Chemother-
apy Questionnaire (BCQ)18 containing 17 items (ques-
tions) was administered by a nurse. The BCQ is a
disease specific instrument for measuring quality of
life in patients with breast carcinoma and previously
has been shown to be valid and reliable.18 The original
instrument, composed of 30 items, was based on the
physical, emotional, and social problems identified by
women receiving adjuvant chemotherapy for breast
carcinoma. In the modified version, 15 items specific
to chemotherapy were omitted, and 2 items specific to
radiation therapy were added. These items were de-
veloped using a similar methodology to that used to
develop the original questionnaire. A preliminary list
of items considered likely to be important to women
receiving breast irradiation was generated through a
review of the literature, consultation with radiation
oncologists and nurses, and structured interviews with
axillary lymph node negative breast carcinoma pa-
tients. Two items (questions) were selected based on
the frequency with which they were reported and the
importance attributed to the item by patients. The first
item was “How much of the time during the past 2
weeks have you been troubled by pain, itchiness, or
discomfort of the skin of your chest?” with responses
on a Likert scale from 1 (all of the time) to 7 (none of
the time). The second item was “How much trouble or
inconvenience have you had during the past 2 weeks
as a result of not being able to bathe or wash your
chest?” with responses on a Likert scale from 1 (a great
deal of trouble or inconvenience) to 7 (no trouble or
inconvenience).
Hence, the version of the BCQ used in our study
contained 6 domains including emotional dysfunction
(6 items), social support (2 items), attractiveness (1
item), fatigue (5 items), physical symptoms (2 items),
2262 CANCER May 15, 2000 / Volume 88 / Number 10
and inconvenience (1 item). Each item was answered
on a 7-point Likert scale, and the mean score of all
items represented a summary score for overall quality
of life.
The BCQ was administered to women at baseline,
1 month (4 weeks) and 2 months (8 weeks) after ran-
domization.
Long term phase (3 months to 2 years after
randomization)
Originally, we intended to administer the BCQ every 3
months for the first 2 years after randomization, but
this turned out to be logistically impractical. Three
items regarding irritation of the skin, breast pain, and
appearance of the breast to the patient were modified
from the original instrument. Specifically, 3 questions
were asked:
1. During the past 2 weeks, have you been troubled
by pain, itchiness, or discomfort of the skin of your
chest?
2. During the past 2 weeks, have you been troubled
or inconvenienced as a result of pain in the breast
that was operated on?
3. During the past 2 weeks, have you been troubled
or upset as a result of feeling upset that the breast
that was operated on is unattractive?
Each of the items had a 4-point Likert scale ranging
from 1 (not at all) to 4 (very often). Items were admin-
istered every 3 months for the first 2 years of the study.
Statistical Methods
Acute quality of life
In the acute phase after randomization, quality of life
scores were calculated for each patient for the entire
17-item BCQ instrument and for the 6 individual do-
mains as means of the available responses. Mean
change scores for each subject were calculated by
subtracting the baseline response from the 2 postran-
domization scores. Only patients who completed the
questionnaires at baseline, 1 month, and 2 months
were included in this analysis. Repeated measures
mixed models were used to compare the effect of
treatment on quality of life and to account for corre-
lated within-person responses.19 Various covariance
structures were considered using SAS (version 6.12)
PROC MIXED. In the model fitting stage, a nominal P
value of ⬍ 0.01 was used to determine statistical sig-
nificance in view of the multiple comparisons per-
formed.
Previous studies using similarly derived instru-
ments to measure quality of life associated with
asthma and chronic lung disease have demonstrated
that mean differences of 0.5, 1, or ⬎ 1 on a 7-point
Likert scale have been associated with small, moder-
ate, or large changes, respectively, in patients’ re-
ported quality of life.20 –22 To help interpret the differ-
ences observed in overall quality of life measured, we
compared the proportion of patients who had deteri-
oration in mean BCQ score ⱖ 0.5 at 2 months relative
to baseline for the control and radiation groups by
using the chi-square test.
Long term quality of life
In the long term phase, the responses to the three
4-point scale questions at 3-month intervals over the 2
years after randomization were dichotomized. A re-
sponse of 3 (occasionally) or 4 (very often) translated
into a negative outcome, whereas a 2 (rarely) or 1 (not
at all) answer was considered to be positive for each of
the three questions on irritation of the skin of the
breast, breast pain, and appearance of the breast to
the patient. The data were summarized in terms of
percent of patients with a negative response. All of the
available long term data were used in this analysis.
Like the acute phase data, repeated measures mixed
models were used to compare the effect of treatment
on irritation of the skin of the breast, breast pain, and
appearance of the breast to the patient and to account
for the within-person correlation.19 Unlike the meth-
ods used for continuous measures, generalized linear
models were fitted to the dichotomized outcomes us-
ing SAS (version 6.12) PROC GENMOD using the Gen-
eralized Estimating Equations (GEE) method of esti-
mation. As above, P values ⬍ 0.01 were declared
statistically significant.
RESULTS
Eight hundred thirty-seven patients were randomly
allocated to receive either radiation (n ⫽ 416) or no
radiation therapy (n ⫽ 421). The treatment groups
were comparable in terms of baseline characteristics,
such as age, tumor size, nuclear grade, and levels of
estrogen and progesterone receptors.15
Acute Quality of Life
Quality of life data at baseline, 1 month, and 2 months
were available for 91% of patients. Fifty-seven percent
of patients started radiation within 2 weeks of ran-
domization. Thus, at the time of the 1 month assess-
ment, 95% of patients were on treatment, and 56% had
completed 2 weeks of treatment. By the 2 month as-
sessment, 88% of patients had completed radiation,
and 58% of patients were more then 2 weeks from the
last radiation treatment. The mean BCQ score over
time for patients in both treatment groups is described
in Figure 1. In the control group, there was a steady
increase in quality of life from baseline to 2 months
 Quality of Life with Breast Irradiation/Whelan et al. 2263

TABLE 2
Mean Change Score (t2–t0) at 2 Months by Domain

Treatment groups

Radiation Control
Domain (n ⴝ 344) (n ⴝ 376) Difference P value

Emotional
dysfunction ⫹0.41 ⫹0.55 ⫺0.14 0.06
Social support ⫺0.32 ⫺0.24 ⫺0.10 0.52
Attractiveness ⫺0.14 ⫹0.05 ⫺0.19 0.03
Fatigue ⫺0.17 ⫹0.28 ⫺0.45 0.0001a
Physical symptoms ⫺1.13 ⫺0.01 ⫺1.12 0.0001a
Inconvenience ⫹0.52 ⫹0.99 ⫺0.47 0.0008a
Overall score ⫺0.05 ⫹0.30 ⫺0.35 0.0001a

a
Statistically significant (P ⬍ 0.01).

FIGURE 1. Mean BCQ score over time and 95% confidence intervals are
shown. BCQ: Breast Cancer Questionnaire.
and attractiveness domains. A similar pattern was ob-
served for the change scores between baseline and 2
TABLE 1
Mean Change Score (t1–t0) at 1 Month by Domain months after randomization (Table 2).
The proportion of patients who had a deteriora-
Treatment groups tion in mean BCQ score of ⱖ 0.5 at 2 months relative
to baseline was compared for the control and radia-
Radiation Control tion groups. Ninety-three of 344 patients (27%) in the
Domain (n ⴝ 344) (n ⴝ 376) Difference P value
radiation group experienced a deterioration in quality
Emotional of life of this magnitude, whereas only 60 of 376 pa-
dysfunction ⫹0.38 ⫹0.42 ⫺0.04 0.57 tients (16%) in the control group experienced a similar
Social support ⫺0.10 ⫺0.21 ⫹0.11 0.34 deterioration (P ⫽ 0.0003).
Attractiveness ⫺0.03 ⫺0.03 0.00 0.97
Fatigue ⫺0.09 ⫹0.15 ⫺0.24 0.005a
Physical symptoms ⫺1.34 ⫺0.04 ⫺1.30 0.0001a
Long Term Quality of Life
Inconvenience ⫺0.26 ⫹0.74 ⫺1.00 0.0001a Approximately 75% of patients responded to the 3
Overall score ⫺0.07 ⫹0.21 ⫺0.27 0.0001a separate items administered during the 2 years after
randomization. The 3-month (12 week) assessment
a
Statistically significant (P ⬍ 0.01).
was performed at a median of 7 weeks after the last
radiation treatment (25–75%, range ⫽ 5.3– 8.7 weeks).
Radiation increased the proportion of patients who
after randomization likely representing patients re- reported being troubled by skin irritation. This was
covering from the effects of diagnosis and surgery. In most evident at the 3-month assessment, 28% in the
the radiation group, the mean score decreased mini- radiation group versus 14% in the control group (P
mally at 1 month and remained relatively unchanged ⫽ 0.0001) (Fig. 2). The number of patients who re-
at 2 months. In terms of mean change score from ported skin irritation decreased over time in both
baseline, at 1 month, the control group increased to groups (P ⫽ 0.0001 for trend) so that by 24 months
⫹0.21 whereas the radiation group decreased by only 7% in each group reported this symptom.
⫺0.07 (Table 1). Similarly, at 2 months, the control With respect to breast pain (Fig. 3), a similar pat-
group increased by ⫹0.30, and the radiation group tern was observed. Radiation therapy increased the
decreased by ⫺0.05 (Table 2). The difference between number of patients who were troubled by breast pain.
groups was statistically significant for both time peri- This was most evident at 6 months after randomiza-
ods (P ⫽ 0.0001). tion in which 33% of patients in the radiation group
To reexamine the effect on individual domains, versus 20% in the control group reported this problem
we looked at the mean change score from baseline for (P ⫽ 0.0002). Again, reporting of this symptom de-
each domain (Table 1). At 1 month, statistically signif- creased over time (P ⫽ 0.0001 for trend), and at 24
icant differences in mean change scores were noted months approximately 15% of patients in both groups
for the fatigue, physical, and inconvenience domains. reported breast pain.
No differences were noted for the emotional, social, With respect to trouble or upset regarding the
2264 CANCER May 15, 2000 / Volume 88 / Number 10

FIGURE 2. Percentage of patients reporting irritation of the skin of the breast FIGURE 3. Percentage of patients reporting breast pain by treatment group
by treatment group is shown. is shown.

appearance of the breast to the patient (Fig. 4), this

was reported less frequently, and no difference was
detected between groups; 4.8% of patients in each
group reported this problem at 2 years (P ⫽ 0.62).

DISCUSSION
In view of the increasing use of breast-conserving
therapy, we were interested in determining the addi-
tional morbidity associated with breast irradiation
from the patient’s perspective. Whereas some studies
have suggested that patients may suffer from anxiety,
depression,12,13 and fatigue16 in addition to local phys-
ical side effects of radiation therapy, other studies
have not shown this effect.15 Our results demonstrate
a difference in overall quality of life between irradiated
and nonirradiated patients during the acute period.
Note that most of the data informing acute quality of
life were collected during or shortly after radiation
therapy. The difference in mean change scores be-
tween groups was 0.27 and 0.35 on a 7-point Likert
scale at 1 and 2 months after randomization, respec-
tively.
When we looked at differences in a mean change
score by domain, no differences were detected be-
tween groups for the domains of emotional dysfunc-
tion, social support, and attractiveness. Statistically
significant differences were observed for the domains
of physical symptoms, inconvenience, and fatigue.
The differences in these 3 latter domains were primar-
ily responsible for the differences observed in the
overall quality of life score for the acute phase. The
differences in these domains are consistent with clin-
ical experience that breast irradiation is associated
FIGURE 4. Percentage of patients reporting trouble or upset regarding the
appearance of the breast by treatment group.
with local physical symptoms and fatigue. These re-
sults also suggest that radiation has little effect on
emotional and social well-being (aside from inconve-
nience).
Although the differences in overall acute quality of
life between groups were statistically significant, the
question arises whether these differences are impor-
tant to patients. Investigators have demonstrated that
mean differences of 0.5, 1, or ⬎ 1 in mean score on a
7-point Likert scale are associated with small, moder-
ate, and large changes, respectively, in patients’ re-
ported quality of life in asthma and chronic lung dis-
ease.20 –22 Similar differences using other quality of life
measures also have been associated with important
changes in cancer patients’ reported quality of life.23
Using these values as a guide, we might interpret the

differences detected in this study between groups in
overall quality of life as not important. If, however, we
look at the number of patients who had a small but
important deterioration in quality of life during the
acute phase (over the 2-month period from random-
ization), a greater number of patients treated with
radiation therapy deteriorated as compared with the
controls. This suggests that whereas the overall mean
difference in acute quality of life detected does not
appear meaningful, 1 in 10 patients had an important
deterioration in quality of life as a result of treatment.
This type of information may be useful for physicians
and patients when discussing the effect of breast irra-
diation after lumpectomy and for treatment decision
making.
Overall quality of life improved in the control
group from baseline to 2 months whereas there was
little change in quality of life in the radiation group
over this 2-month period. The observed difference
between groups may be due either to a more rapid
resolution of postoperative effects in the control pa-
tients or to specific side effects associated with radia-
tion therapy. It is likely that both factors are involved.
Unfortunately, we do not have definitive overall qual-
ity of life data beyond the limited 2-month period to
state that the observed early difference between
groups resolves over time. However, we anticipate that
irradiated patients ultimately attain the same quality
of life as patients who did not receive radiation. This is
supported by the observed decrease in the number of
patients reporting symptoms of skin irritation and
breast pain after radiation treatment.
Results from the three items measured long
term suggest that skin irritation and breast pain
attributed to radiation therapy may be reported up
to 3– 6 months after initiation of treatment. It is
important to note that these symptoms were also
present in nonirradiated patients and continue to
exist in a small proportion of patients up to 2 years
after treatment.
In previous studies of breast-conserving therapy,
cosmetic outcome often has been assessed by an ob-
server, usually a physician. The cosmetic outcome
usually is scored excellent, good, fair, or poor.24 –26 The
overall objective of our study was to examine the
impact of radiation treatments on a patient’s quality
of life. We used a patient-based approach to develop a
questionnaire to assess the impact of cosmetic out-
come on quality of life. This questionnaire is not com-
parable to previous cosmetic rating scales and can be
considered similar to quality of life instruments as-
sessing appearance and body image. Other studies
have reported on factors associated with patients sat-
isfaction with cosmetic outcome. Our study was not
Quality of Life with Breast Irradiation/Whelan et al. 2265
designed to look specifically at factors that affect a
woman’s feelings about breast appearance, but pre-
sumably factors associated with patient satisfaction
with cosmetic outcome, e.g., breast size and shape,
contribute to this outcome.26
Concern regarding the appearance of the breast
was reported equally by both groups and tended to
decrease over time. Breast irradiation delivered with
relatively modern techniques did not result in an im-
portant deterioration in cosmetic outcome from the
patient’s perspective during the 2-year follow-up.
These observations are reassuring because many of
the late effects of radiation injury may be evident by
this time.27 As late sequelae of radiation may progress
beyond 2 years, further follow-up will be necessary to
be confident about this observation.
This study is unique in that it represents the first
randomized trial to our knowledge to report the
quality of life associated with breast irradiation after
lumpectomy in a large number of patients. How-
ever, some conditions should be noted. Radiation
therapy to the whole breast and boost therapy were
delivered with cobalt-60 at 2.5 Gy per fraction. This
approach is not commonly used throughout North
America at the current time; however, the results are
likely to be generalizable to more conventionally
used treatment strategies and fractionation sched-
ules.27 Unfortunately, detailed quality of life infor-
mation was available only for the first 2 months of
follow-up and other indices for only 2 years. Results
from the BCQ indicate that differences in quality of
life between radiation and control groups can be
detected up to 2 months after randomization. Re-
sults from the single items administered for 2 years
suggest that this effect may be more prolonged. In
future studies, more detailed information regarding
the longer term impact of treatment on patients’
overall quality of life would be useful.
In summary, our results demonstrate that radia-
tion therapy did impact on the quality of life of women
with early breast carcinoma during treatment. After
completion of treatment, irradiated patients reported
increased breast symptoms compared with nonirradi-
ated patients. These differences decreased over time.
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