Int. J. Radiation Oncology Biol. Phys., Vol. 68, No. 2, pp. 364 –369, 2007
Copyright © 2007 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/07/$–see front matter
doi:10.1016/j.ijrobp.2006.12.027
CLINICAL INVESTIGATION
Breast
BREAST CANCER PATIENTS WITH 10 OR MORE INVOLVED AXILLARY
LYMPH NODES TREATED BY MULTIMODALITY THERAPY: INFLUENCE
OF CLINICAL PRESENTATION ON OUTCOME
FADY B. GEARA, M.D., PH.D.,* ELIE NASR, M.D.,* SUSAN L. TUCKER, PH.D.,¶
MAYA CHARAFEDDINE, M.S.,† BOUTHAINA DABAJA, M.D.,* TOUFIC EID, M.D.,* JABER ABBAS, M.D.,‡
ZIAD SALEM, M.D.,§ ALI SHAMSEDDINE, M.D.,§ PHILIP ISSA, M.D.,* AND NAGI EL SAGHIR, M.D.§
Departments of *Radiation Oncology, †Epidemiology and Biostatistics, ‡General Surgery, and §Medical Oncology, The American
University of Beirut Medical Center, Beirut, Lebanon; ¶Department of Biomathematics, The University of Texas, M. D. Anderson
Cancer Center, Houston, TX
Purpose: To analyze tumor control and survival for breast cancer patients with 10 or more positive lymph nodes
without systemic disease, treated by adjuvant radiation alone or combined-modality therapy.
Methods and Materials: We reviewed the records of 309 consecutive patients with these characteristics who
received locoregional radiotherapy (RT) at our institution. The majority of patients had clinical Stage II or
IIIA–B disease (43% and 48%, respectively). The median number of positive axillary lymph nodes was 15 (range,
10 –78). Adjuvant therapy consisted of RT alone, with or without chemotherapy, tamoxifen, and/or ovarian
castration.
Results: The overall 5-year and 10-year disease-free survival (DFS) rates were 20% and 7%, respectively. Median
DFS was higher for patients with Stage I–II compared with those with Stage IIIABC (28 vs. 19 months; p ⴝ
0.006). Median DFS for patients aged <35 years was lower than that of older patients (12 vs. 24 months; p <
0.0001). Patients treated with a combination therapy had a higher 5-year DFS rate compared with those treated
by RT alone (26% vs. 11%; p ⴝ 0.03). In multivariate analysis, clinical stage (III vs. I, II; relative risk ⴝ 1.8, p
ⴝ 0.002) and age (<35 vs. others; relative risk ⴝ 2.6, p <0.001) were found to be independent variables for DFS.
Conclusion: This retrospective data analysis identified young age and advanced clinical stage as pertinent and
independent clinical prognostic factors for breast cancer patients with advanced axillary disease (10 or more
involved nodes). These factors can be used for further prognostic classification. © 2007 Elsevier Inc.
Breast cancer, Advanced disease, Clinical presentation.
INTRODUCTION
adjuvant treatment strategies to fit this risk classification (2,
5, 6). Recognizing the high risk of recurrence for patients
with more than 10 positive axillary lymph nodes, several
research groups have investigated aggressive treatment approaches, such as intensified chemotherapy regimens with
stem cell support for this patient population (7–12). Unfortunately, these aggressive approaches did not result in an
unequivocal clinical benefit, and the quest for an appropriate
adjuvant therapy for these high-risk patients remains ongoing (13).
Over the years, clinical investigations of breast cancer
have identified important prognostic factors and developed
different chemotherapy regimens, drug combinations, and
strategies, with or without hormonal therapy, and with or
without locoregional radiotherapy (LRRT) to address the
individual risk of recurrence. Whereas early studies considered LRRT a potentially harmful treatment owing to exces-
Despite increased awareness and early detection campaigns,
many patients with breast cancer still present with locally
and regionally advanced disease. In patients with breast
cancer, the risk of axillary lymph node involvement is
directly related to the size of the tumor; however, the
number of involved axillary lymph nodes is relatively independent of tumor size and location within the breast (1).
It has been widely accepted that the presence of positive
axillary metastases is the most important prognostic factor
in breast cancer (2, 3). Within the group of patients with
positive axillary lymph nodes, those who have a higher
number of involved nodes have a worse outcome (1, 3, 4).
In view of this, several studies have identified separate
clinical prognostic groups based on the number of involved
axillary lymph nodes (e.g., ⬍3, 4 –7, ⬎7) and proposed
Reprint requests to: Fady B. Geara, M.D., Ph.D., Department of
Radiation Oncology, American University of Beirut, 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017-2303. Tel: (⫹961)
1-344839; Fax: (⫹961) 1-370795; E-mail: fg00@aub.edu.lb
Conflict of interest: none.
Received Nov 3, 2006, and in revised form Dec 8, 2006.
Accepted for publication Dec 9, 2006.
364
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Breast cancer with ⱖ10 involved axillary lymph nodes ● F. B. GEARA et al.
sive non– cancer-related deaths (14), the publication of two
prospective, randomized trials later demonstrated that postmastectomy radiotherapy (RT) reduces both locoregional
recurrence and mortality from breast cancer in patients with
high risk of recurrence (15, 16). The actual contribution of
LRRT for patients with advanced breast cancer was also
evaluated by Strom et al. (17), who reported on 376 patients
with advanced breast cancer treated by surgery and RT
without chemotherapy between 1955 and 1984. They observed a 5-year disease-specific survival (DSS) rate of 48%
and 30% for patients with stage IIIA and IIIB, respectively,
indicating that LRRT contributes to a survival benefit in this
group of patients because a reasonable proportion of patients can be cured by locoregional therapy alone.
Few studies have examined locoregional therapies in
breast cancer patients with 10 or more positive axillary
lymph nodes. Donegan and Lewis (4) have demonstrated
that patients with more than 10 involved lymph nodes,
treated with radical mastectomy alone, had a locoregional
recurrence rate of 50% and a 10-year survival rate of 10%.
Diab et al. (18) analyzed 618 breast cancer patients with
⬎10 positive axillary lymph nodes and reported a survival
advantage in those patients receiving postmastectomy RT.
Similar results were reported by Jabro et al. (19), who
analyzed the outcome of 55 patients with 10 or more positive axillary lymph nodes treated by intensive chemotherapy, including high-dose chemotherapy and stem cell transplantation with or without LRRT. Although the addition of
systemic therapy and LRRT has improved the prognosis of
these high-risk patients, the optimal integration, intensity,
and relative benefit of the various therapeutic options remains unclear.
In this study, we review the results of breast cancer
management in patients with ⱖ10 positive axillary nodes
and without systemic disease at our institution. Particular
attention is focused on the respective role of each adjuvant
treatment modality and on potential prognostic factors
within this group of high-risk patients.
METHODS AND MATERIALS
Patient population
The medical records of all patients with node-positive breast
cancer, referred for RT at our institution between 1966 and 1997,
were reviewed. A total of 309 patients had 10 or more positive
axillary lymph nodes without evidence of distant metastases and
were included in the analysis. Data were retrospectively collected
on clinical characteristics, clinical and surgical staging, RT parameters, adjuvant chemotherapy, and hormonal therapy, including
ovarian castration. Demographic and follow-up information and
data on time and sites of recurrence were obtained by direct review
of the medical records performed by the investigators.
Treatment methods
All patients underwent surgery. Modified radical mastectomy
was performed in 181 patients (59%), radical mastectomy in 116
(38%), partial mastectomy in 8 (2%), and simple mastectomy in 4
patients (1%). Adjuvant therapy consisted of RT alone in 94
365
Table 1. Patient and treatment characteristics
Parameter
Number (percentage)
Age ⬍50 y
Age ⱖ50 y
Stage
I
II
IIIAB
IIIC
Pathologic types
Invasive ductal Ca
Invasive lobular Ca
Scirrhous Ca
Medullary Ca
Pathology grade
High
Intermediate
Low
Not specified
Type of surgery
Radical
Modified radical
Simple
Partial
Adjuvant therapy
Radiation alone
RT/ovarian castration alone
RT/tamoxifen alone
RT/chemotherapy
Chemotherapy regimens
CMF
FAC
Other
169 (55)
140 (45)
8 (3)
132 (43)
149 (48)
19 (6)
288 (93)
8 (3)
10 (3)
3 (1)
111 (36)
53 (17)
8 (3)
137 (44)
116 (38)
181 (59)
4 (1)
8 (2)
94 (30)
15 (5)
17 (6)
183 (59)
41 (22)
68 (37)
74 (41)
Abbreviations: Ca ⫽ carcinoma; RT ⫽ radiotherapy; CMF ⫽
cyclophosphamide-methotrexate-5-fluorouracil; FAC ⫽ 5-fluorouracil-adriamycin-cyclophosphamide.
Note: Patients aged ⬎50 years were arbitrarily considered
postmenopausal.
patients (30%), RT with ovarian castration and no chemotherapy in
15 (5%), RT with tamoxifen and no chemotherapy in 17 (6%). A
total of 183 patients (59%) received adjuvant chemotherapy, which
consisted of CMF (cyclophosphamide-methotrexate-5-fluorouracil) in 40 patients (13%), FAC (5-fluorouracil-adriamycin-cyclophosphamide) in 30 patients (10%), or other types of single or
multiagent chemotherapy in 113 patients (37%), with or without
ovarian castration or tamoxifen. The decision to deliver ovarian
castration depended on the physician and the time period during
which the patient was treated. A total of 51 patients (17%) received
radiotherapeutic ovarian castration with a median pelvic radiation
dose of 24 Gy (range, 14 –25 Gy) (Table 1). Adjuvant RT was
delivered to the entire chest wall, ipsilateral axillary and supraclavicular (SCV) regions, and internal mammary nodes (IMN). The
radiation technique was quite uniform, using opposed tangents to
treat the chest wall and a single appositional field to treat both the
IMN and SCV nodes. The large majority of the patients (302;
98%) received RT to all four volumes (chest wall, axilla, IMN, and
SCV region); in 4 patients (1%) the SCV region was omitted; and
in another 3 patients (1%) the chest wall was omitted. The median
dose to the chest wall was 56 Gy (range, 44.6 – 68 Gy) delivered at
2 Gy per fraction using Co60 photons. The median doses to
different target volumes were as follows: SCV region, 55 Gy
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I. J. Radiation Oncology ● Biology ● Physics
Proportion of patients
1
axillary lymph nodes was 15 (range, 10 –78). The median
ratio of positive to recovered axillary nodes was 0.81
(range, 0.18 –1).
FLRF
0.75
0.5
FDM
0.25
0
DFS
0
2
4
Volume 68, Number 2, 2007
6
8
10
Time (years)
Fig. 1. Actuarial rates of freedom from locoregional failure
(FLRF), freedom from distant metastases (FDM), and disease-free
survival (DFS).
(range, 41–75 Gy); internal mammary chain, 55 Gy (range, 41– 66
Gy); and axilla, 55.8 Gy (range, 41–76 Gy). No chest wall scar
boost was delivered.
Statistical analysis
The median follow-up time among censored patients was 11
months (range, 1–172 months). Local, regional, or systemic recurrences were detected clinically by imaging or laboratory tests
performed either during routine follow-up visits or for specific
symptoms. Overall survival, DSS and disease-free survival (DFS)
were analyzed in relation to various patient and tumor characteristics using univariate and multivariate analyses. Because many
patients were living at the time they were lost to follow-up, DFS
is used for all survival figures and all univariate and multivariate
analyses. Univariate analyses were performed using the log–rank
test, and multivariate analyses were performed using the Cox
proportional hazards model with both forward and backward stepwise procedures.
RESULTS
Patient characteristics
The median age was 48 years (range, 26 – 85 years). One
hundred sixty-nine patients (55%) were aged ⬍50 years and
for the purpose of this analysis were arbitrarily considered
premenopausal, with the remaining 140 patients aged ⱖ50
years considered postmenopausal. Only 22 patients (7%)
reported a positive family history of breast cancer in firstdegree relatives. The patients’ clinical stage distribution
was as follows: Stage I, 8 patients (3%); Stage II, 132
(43%); Stage IIIA–B, 149 (48%); and Stage IIIC, 19 (6%)
(patients with positive ipsilateral SCV lymph nodes). Pathologic examination revealed predominant invasive ductal
carcinoma (93%), whereas few patients showed scirrhous
carcinoma (3%), invasive lobular carcinoma (3%), or medullary carcinoma (1%). The majority of tumors with known
grades were high grade (64%), followed by intermediate
grade (31%), and low grade (5%) (Table 1). Information
regarding hormonal receptors was only available for 47
patients (15%), for whom estrogen receptors were positive
in 53% and progesterone receptors were positive in 49%;
both receptors were positive in 43% and both were negative
in 40% of these patients. The median number of positive
Survival rates and prognostic factors
Actuarial DFS rates at 5 and 10 years were 20% and 0.
Freedom from locoregional recurrence at 5 and 10 years
was 76%. Freedom from distant failure at the same time
points was 24% and 9%, respectively (Fig. 1). Univariate
analysis was performed to identify prognostic variables for
DFS. This analysis included several patient-, treatment-,
and tumor-related factors and identified clinical stage, age,
and type of adjuvant therapy as significant prognostic factors for DFS; menopausal status, number of lymph nodes,
and treatment era were not significant prognostic factors.
The median DFS was 28 months for patients with Stage I–II
disease, compared with 19 months for those patients with
Stage IIIAB–IIIC disease (p ⫽ 0.006) (Fig. 2). Classification and regression tree analysis identified age of 35 years as
a prognostic cut point. The median DFS for patients aged
ⱕ35 years was 12 months, compared with 24 months for
those aged ⬎35 years (p ⬍ 0.0001) (Fig. 3). Patients treated
with trimodality adjuvant therapy with a combination of
RT, chemotherapy, and hormonal therapy (tamoxifen with
or without ovarian castration) had the highest 5-year DFS
rate compared with those treated by RT alone (26% vs.
11%; p ⫽ 0.03) (Fig. 4). However, menopausal status
(arbitrarily defined as age ⬍50 or ⱖ50 years) was borderline significant (p ⫽ 0.051), and the number of positive
lymph nodes was not significant for DFS whether it was
tested as a continuous variable (p ⫽ 0.71) or cut at the
median (ⱕ15 vs. ⬎15; p ⫽ 0.23). Median DFS times by
treatment era were not statistically different (1966 –1977: 26
months; 1978 –1987: 22 months; 1988 –1997: 22 months; p
⫽ ns). The type of chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil [CMF] vs. 5-fluorouracil-adriamycin-cyclophosphamide [FAC] vs. any other combination)
also had no influence on DFS (p ⫽ 0.64). Similarly, there
was no evidence of any effect of ovarian castration when all
patients were considered (p ⫽ 0.83), or for patients aged
⬍50 years who did not receive chemotherapy (p ⫽ 0.52), or
those aged ⬍50 years who received chemotherapy (p ⫽
0.75). Patients who received adjuvant RT alone had a 5-year
1
Proportion of patients
366
p<0.001
0.75
0.5
Stage I-II
0.25
III-IV
0
0
2
4
6
Time (years)
8
10
Fig. 2. Disease-free survival as a function of clinical disease
stage.
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p<0.0001
1
0.75
>35 yrs
0.5
0.25
0
≤ 35 yrs
0
2
4
6
Time (years)
8
10
Fig. 3. Influence of patient age on disease-free survival. Age 35
years was identified as a prognostic cut point according to classification and regression tree analysis.
DFS rate of 11% (Fig. 4). This indicates that a minority of
patients in this high-risk category can be cured by locoregional therapy only.
Using a Cox regression analysis, clinical stage (IIIABC
vs. I, II; relative risk [RR] ⫽ 1.8, p ⫽ 0.002) and age (ⱕ35
years vs. others; RR ⫽ 2.6, p ⬍ 0.001) were identified as
independent prognostic factors for DFS. However, the types
of therapy (multimodality with RT and chemotherapy [any
regimen] and hormonal therapy [tamoxifen with or without
ovarian castration] vs. RT alone) were not significantly
different in multivariate analysis (RR ⫽ 0.692 [0.427–
1.121], p ⫽ 0.13) (Table 2). Ovarian castration alone had no
influence on DFS, regardless of age or use of adjuvant
chemotherapy (p ⫽ 0.83).
DISCUSSION
In this study, we report the characteristics and treatment
results of breast cancer patients with 10 or more axillary lymph
nodes without systemic metastases on presentation. This group
of patients received various combinations of adjuvant therapy
that varied primarily with the period during which treatment
was administered but also with the preference of the managing
physician(s). Our results indicate that even in this group of
high-risk patients, clinical stage and age remain powerful prognostic factors that could allow for further risk classification and
individual risk-adapted therapy. Another interesting but more
intuitive finding was a superior outcome for patients who
received trimodality adjuvant therapy in comparison with those
who received adjuvant RT alone (univariate analysis). The
patients who received RT alone as adjuvant therapy had a poor
(11%) 5-year DFS rate, indicating that only a very small
proportion of these high-risk patients can be cured by locoregional therapy alone.
Few studies have specifically examined the outcome of
this group of breast cancer patients with 10 or more involved axillary lymph nodes (7–12, 18 –20). The majority of
these reports were randomized trials evaluating the therapeutic benefit of high-dose chemotherapy and stem cell
transplantation for this high-risk patient group (7–12, 20).
Most of these studies included chest wall RT for all patients,
and, therefore, evaluation of the additional impact of RT is
not possible. The largest study that examined the effect of
RT with particular attention was reported by Diab et al.
367
(18), who analyzed the outcome of 618 breast cancer patients with 10 or more positive axillary lymph nodes treated
by systemic therapy with or without RT. The investigators
found a significant benefit from RT on local failure (13% vs.
38%, p ⫽ 0.0001), distant failure (48% vs. 58%, p ⫽ 0.02),
and overall survival (58% vs. 42%, p ⫽ 0.001) in favor of
the group of patients who received RT. Jabro et al. (19)
reported on 55 patients with 10 or more involved axillary
lymph nodes, treated by systemic chemotherapy with or
without RT. Findings similar to those published by Diab et
al. were reported, with the group receiving adjuvant RT
having less locoregional recurrences and better DFS. In the
present study, 30% of the patients received RT alone as their
adjuvant therapy, and 11% of them remained disease free at
5 years. Although this result seems rather low, it still supports the idea that not all patients with high-risk breast
cancer present with systemic disease at diagnosis and that
LRRT does provide some survival benefit because a certain
proportion of patients, albeit small, can be cured by locoregional therapy alone. This small but definite survival increment provided by adjuvant RT is well demonstrated in the
milestone Danish and British Columbia postmastectomy
radiation trials (15, 16). It is of interest to note that in both
trials, as in our study, all patients were treated to the IMC
nodes. However, the significance of this observation and the
value of elective IMC radiation remain unknown and are
beyond the scope of this study. Further support to the notion
that adjuvant RT alone could be curative in locoregionally
advanced breast cancer is provided by the study of Strom et
al. (17), who reported on 376 patients with advanced breast
cancer treated with surgery and RT without chemotherapy
between 1955 and 1984. The 5-year DSS rate was 48% and
30% for patients with stage IIIA and IIIB, respectively,
indicating that locoregional therapy alone was curative in a
good proportion of these patients.
There is a general assumption in breast cancer management that once the number of positive axillary lymph nodes
reaches 10 or more, other clinical or pathologic parameters
may become irrelevant. In the present study, in which all
patients had 10 or more positive axillary lymph nodes,
young age and clinical stage were found to be strong and
independent determinants of outcome. Both parameters
have long been recognized as strong prognostic factors in
Proportion of patients
Proportion of patients
Breast cancer with ⱖ10 involved axillary lymph nodes ● F. B. GEARA et al.
1
p= 0.03
0.75
0.5
RT/CT/HT
0.25
RT alone
0
0
2
4
6
Time (years)
8
10
Fig. 4. Influence of type of adjuvant therapy on disease-free
survival. RT ⫽ radiotherapy; CT ⫽ chemotherapy; HT ⫽ hormonal therapy.
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I. J. Radiation Oncology ● Biology ● Physics
368
Volume 68, Number 2, 2007
Table 2. Results of univariate and multivariate analyses for prognostic factors
Parameter
Univariate
Age (y)
Stage
Type of adjuvant therapy
Menopausal status
Number of positive lymph nodes
Type of chemotherapy
Multivariate
Age (y)
Stage
Strata
Hazard ratio (CI)
p
ⱕ35 vs. ⬎35
I–II vs. IIIAB–IIIC
RT alone vs. trimodality
Pre- vs. postmenopausal
Continuous variable,
⬍ median vs. ⱖ median (15)
CMF vs. FAC vs. other
⬍0.0001
⬍0.001
0.03
0.051
0.71
0.23
0.64
ⱕ35 vs. ⬎35
I–II vs. IIIABC
⬍0.001
0.015
2.67 (1.67–4.27)
1.58 (1.09–2.28)
Abbreviations: CMF ⫽ cyclophosphamide-methotrexate-5-fluorouracil; FAC ⫽ 5-fluorouracil-adriamycin-cyclophosphamide; CI ⫽ 95%
confidence interval.
Note: Premenopausal status was arbitrarily defined as age ⱕ50 years.
tion and providing risk-adapted therapy for this high-risk
patient population.
The survival benefit of adjuvant chemotherapy has long
been recognized and documented for breast cancer (21).
This is also the case for adjuvant hormonal therapy for
patients with positive estrogen receptor status (21) and for
LRRT (15, 16, 22). Furthermore, meta-analyses data have
shown that the addition of all three modalities results in a
true additive effect. In our study, univariate analyses revealed that the best outcome was observed in those patients
who received all three treatment modalities, irrespective of
the type of chemotherapy regimen (Fig. 4). This effect of
combined adjuvant therapy was not shown in multivariate
analysis, which suggests that the possibility of a favorable
confounding variable may still exist. One potential selection
bias is the existence of positive estrogen receptors in those
patients who received triple adjuvant therapy. Indeed, several studies conducted on this high-risk group have shown
that patients with positive estrogen receptors have a better
outcome (8, 10, 18, 20). Unfortunately, because patients
enrolled in this review were treated as far back as 1966,
the information on estrogen receptor status is only available for a small group of patients, and, therefore, it is not
1
Proportion of patients
breast cancer and are often considered clinical criteria for
patient eligibility and risk stratification in many clinical
studies. The additive value on prognostic classification of
these two parameters in this high-risk population could be
of great clinical interest, and data from other studies are in
agreement with our findings (10, 18, 20). In a randomized
study by Thallman et al. (10) on high-dose chemotherapy
and stem cell transplantation, patients aged ⬍40 years demonstrated a worse outcome than older patients. In a similar
study by Nitz et al. (20), the investigators found that age
⬍35 years was an adverse prognostic factor but only in
patients receiving the conventional chemotherapy regimen.
Similarly, several studies have reported that stage (or tumor
size) demonstrate an independent prognostic effect on outcome in this high-risk patient population (8, 11, 18, 20).
Schrama et al. (11) conducted a study in which patients with
10 or more positive axillary lymph nodes were randomized
between adjuvant conventional chemotherapy and highdose chemotherapy with stem cell transplantation. Cox regression analysis identified T stage and the number of
positive lymph nodes after neoadjuvant chemotherapy as
having an independent impact on DFS. Zander et al. (8)
conducted a similar trial in the same patient population, and
found T size (⬎3 cm), negative estrogen receptors, and
Grade 3 differentiation to be adverse prognostic factors. In
the study by Nitz et al. (20), patients were enrolled if they
had 9 or more positive axillary lymph nodes, and those who
had a tumor size ⬎4 cm demonstrated a worse outcome
only if they were receiving the conventional treatment.
Tumor size was not significant in those patients who received the experimental high-dose treatment. Negative estrogen receptors and a poor differentiation grade showed the
same effect. Diab et al. (18) found that T stage and age were
also independent predictors of survival. In that study, receptor status, number of positive axillary lymph nodes, and
the addition of RT were also found to be independent
predictors of overall survival. Our results are in agreement
with results from these studies regarding the prognostic
value of age and stage, which lends more support to the use
of these two clinical parameters in refining risk classifica-
p= 0.02
0.75
Favorable group
0.5
0.25
Unfavorable group
0
0
2
4
6
8
10
Time (years)
Fig. 5. Disease-free survival for patients with favorable vs. unfavorable prognostic features. Patients in the favorable group were
aged ⬎35 years, with Stage I–II disease, and received all three
types of adjuvant therapies. All other patients were considered to
be in the unfavorable group.
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Breast cancer with ⱖ10 involved axillary lymph nodes ● F. B. GEARA et al.
possible to verify whether the existence of estrogen receptors was indeed a favorable selection bias for this
group of patients.
In light of these findings, one could question the premise
that all breast cancer patients with 10 or more positive axillary
lymph nodes invariably have a poor prognosis. Indeed, within
our patient population, those with all favorable features (age
⬎35 years, Stage I–II clinical stage, treated by triple modality
adjuvant therapy) have a 5-year DFS rate of 45%, compared
with 19% for all other patients (Fig 5). This indicates that some
of the patients with favorable prognostic features still have a
reasonable outcome, despite their high number of positive
axillary lymph nodes. Although this might seem a simplified
prognostic classification based on straightforward clinical pa-
369
rameters, it still adds to existing methods of risk stratification.
With the advent of more complex biologic and genetic profiling, it would be expected that this risk stratification would
continue to be further improved and that more prognostic
subgroups could be identified within this high-risk population.
In summary, this retrospective study on breast cancer
patients with 10 or more positive axillary lymph nodes
without systemic disease identified young age (ⱕ35 years)
and advanced clinical stage (IIIAB and IIIC) as important
and independent clinical prognostic factors. These clinical
factors can be used for further prognostic classification and
risk-adapted adjuvant therapy. Our findings also suggest
that this group of high-risk patients would benefit from
maximal trimodality adjuvant therapy.
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