ArticlePDF Available

Lymphovascular Invasion, as a Prognostic Marker in Patients with Invasive Breast Cancer

Authors:
Gunay Gurleyik at Haydarpasa Numune Research and Teaching Hospital
Gunay Gurleyik
Emin Gurleyik at Duzce University
Emin Gurleyik
Fugen Vardar Aker at Haydarpasa Numune Educatıon and research hospıtal
Fugen Vardar Aker
  • Haydarpasa Numune Educatıon and research hospıtal
Ali Aktekin at Giresun University
Ali Aktekin
Show all 7 authorsHide
Download full-text PDF
Read full-text
Download citation

Abstract

The markers of prognosis are used to predict the clinical course of disease and the outcome for patients with invasive breast cancer. Our aim is to investigate the relationship of peritumoural lymphovascular invasion (LVI) with well-known prognostic markers. Eighty-one surgically treated patients with invasive breast cancer were evaluated in this study during a mean follow-up period of 46 months (12-72). The patient's age (menopausal status), tumour size, nuclear grade, axillary lymph node involvement, and hormone receptor status were determined as markers of the prognosis. The relationship of LVI with these markers was established. Except for menopausal status (p = 0.25) a close relationship was found between the presence of LVI and studied prognostic factors. LVI was positive in 29% of T1, 54% of T2 (p = 0.028) and 100% of T3 tumours (p = 0.002). The rate of LVI (+) has increased gradually as 0%, 38% and 77% (p = 0.001) with grades 1, 2 and 3 respectively. Positive LVI has been determined in 85% (p < 0.0001) and 73% (p = 0.0004) of oestrogen and progesterone receptor negative tumours respectively. LVI was present in 14% and 73% (p < 0.0001) of patients with negative and positive axilla respectively. Metastatic cancer caused mortality in seven patients of whom 86% had more than four involved axillary nodes, and 100% LVI (+). The high rate of positive LVI shows a close relationship with known markers of poor prognosis. The presence of LVI can predict a worse outcome for patients with invasive breast cancer. LVI may be used as an indicator of aggressive behaviour, metastatic ability (nodal and systemic) of the primary malignancy.
Content uploaded by Ali Aktekin
Author content
All content in this area was uploaded by Ali Aktekin on Jul 25, 2014
Content may be subject to copyright.
Acta chir belg, 2007, 107, 284-287
Introduction
Prognostic factors can be used to predict the natural his-
tory of breast cancer. The decision to apply adjuvant
aggressive systemic therapy might be warranted in
patients whose prognosis is poorly predicted by using
prognostic factors. The presence or absence of metasta-
tic involvement in axillary lymph nodes, tumour size,
nuclear grade, hormone receptor status, and patient’s age
are well known prognostic factors for patients with inva-
sive breast cancer. Lymph node involvement with the
tumour cells is accepted as the most powerful prognos-
tic factor (1, 2). Lymph node involvement reveals that
the malignancy has gained the ability of systemic spread
and the risk of distant metastasis increases. The presence
of tumour emboli within peritumoural endothelial lined
spaces was defined as lymphovascular invasion (LVI).
The identification of LVI may permit the determination
of patients at increased risk for axillary involvement and
distant metastases (2, 3).
The aim of this study was to investigate the relation-
ship of LVI with well-known prognostic markers and its
predictive role on axillary lymph node involvement and
outcome (prognosis) of breast cancer cases.
Materials and Methods
We evaluated 81 patients with invasive breast cancer in
this study during a mean follow-up period of
46 months (12-72). They have been surgically treated by
modified radical mastectomy or by wide local excision
and sentinel node biopsy followed by axillary dissec-
tion. The tumour size was measured macroscopically.
Nuclear grade was determined by a modification of the
simplified Black technique. Axillary status was evaluat-
ed by sentinel lymph node biopsy and by level 1 and 2
axillary dissection. Lymph nodes were identified and
stained with haemotoxilen eosin and examined for
tumour metastasis. Hormone receptor status was deter-
mined by immunohistochemistry. Tumour and peri-
tumoral breast tissue was examined for lymphovascular
invasion. The presence of tumour emboli within
peritumoural endothelial lined spaces, stained with H
and E is defined as positive LVI in accordance with the
Lymphovascular Invasion, as a Prognostic Marker in Patients with Invasive
Breast Cancer
G. Gurleyik*, E. Gurleyik**, F. Aker***, A. Aktekin*, S. Emir*, O. Gungor*, A. Saglam*
Departments of Surgery* and Pathology***, Haydarpasa Numune Education and Research Hospital, Istanbul ;
Department of Surgery**, AIBU Duzce Medical Faculty, Duzce, Turkey.
Key words. Breast cancer ; axilla ; lymphovascular invasion ; metastasis.
Abstract. Purpose : The markers of prognosis are used to predict the clinical course of disease and the outcome for
patients with invasive breast cancer. Our aim is to investigate the relationship of peritumoural lymphovascular invasion
(LVI) with well-known prognostic markers.
Patients and Methods : Eighty-one surgically treated patients with invasive breast cancer were evaluated in this study
during a mean follow-up period of 46 months (12-72). The patient’s age (menopausal status), tumour size, nuclear
grade, axillary lymph node involvement, and hormone receptor status were determined as markers of the prognosis. The
relationship of LVI with these markers was established.
Results : Except for menopausal status (p = 0.25) a close relationship was found between the presence of LVI and stud-
ied prognostic factors. LVI was positive in 29% of T1, 54% of T2 (p = 0.028) and 100% of T3 tumours (p = 0.002). The
rate of LVI (+) has increased gradually as 0%, 38% and 77% (p = 0.001) with grades 1, 2 and 3 respectively. Positive
LVI has been determined in 85% (p < 0.0001) and 73% (p = 0.0004) of oestrogen and progesterone receptor negative
tumours respectively. LVI was present in 14% and 73% (p < 0.0001) of patients with negative and positive axilla respec-
tively. Metastatic cancer caused mortality in seven patients of whom 86% had more than four involved axillary nodes,
and 100% LVI (+).
Conclusion : The high rate of positive LVI shows a close relationship with known markers of poor prognosis. The pres-
ence of LVI can predict a worse outcome for patients with invasive breast cancer. LVI may be used as an indicator of
aggressive behaviour, metastatic ability (nodal and systemic) of the primary malignancy.
LVI, Prognostic Marker for Breast Cancer 285
guidelines outlined by PAGE and ANDERSON (4). Studied
markers of prognosis were classified according to the
presence of LVI in order to establish the relationship of
LVI with other markers.
Statistical analysis
Variables were analyzed using Fisher’s exact test.
Univariate analyses of variance were performed by
Post-hoc test. A p value of less than 0.05 was considered
as significant.
Results
The mean age of patients at the time of surgery was
55.5 years. Thirty patients (37%) were premenopausal.
Oestrogen and progesterone receptors were positive in
55 (68%) and 51 (63%) patients respectively. The differ-
ence of LVI (+) was significant according to hormone
receptors status. The rate of LVI (+) has increased pro-
portionally and gradually with tumour size and the
nuclear grade of primary tumour. Forty-five patients
(56%) had axillary involvement. LVI was present in
33 patients (73%) with lymph node metastases (p <
0.0001). Only five patients (14%) had LVI positive
tumours in the node negative group (Table I). LVI was
positive in all patients with a tumour larger than 5 cm
and who had more than ten metastatic lymph nodes. The
rate of positive LVI has gradually increased according to
more serious indicators of poorer prognosis (Table II).
Seven patients, who died from metastatic breast
cancer during the follow-up period, had lymph node
involvement and LVI (+) tumours. Five patients (71%)
were premenopausal, and five (71%) had grade 3
tumour. Six patients (86%) had more than four involved
nodes, and six tumours (86%) were hormone receptor
negative. All seven patients (100%) had LVI (Table III).
Discussion
Previous well-designed studies have analyzed the prog-
nostic factors in patients with invasive breast cancer for
determining the subgroup of patients who have biologi-
cally aggressive tumours. Axillary lymph node involve-
ment, younger age, high nuclear grade, large tumour
size and the absence of hormonal receptors were signif-
icantly correlated with poor disease-free and overall
survival (1). LVI has also been determined to be a
significant negative predictor of prognosis in previous
studies (2, 3, 5). We tried to assess the relationship of
the presence or absence of LVI in tumoral or peritumoral
tissue with known prognostic factors of breast cancer
in our patients.
The prognosis of invasive breast cancer is known to
be poorer in premenopausal women (1, 6, 7). The short-
term follow-up in our study has confirmed aggressive
behavior of breast cancer in younger people. Five (71%)
of our seven patients who died from metastatic disease
were premenopausal. Although the difference was not
significant, a higher rate of LVI (+) tumours in younger
patients has indicated tumour aggressiveness. Based on
our results, the presence of LVI is not so significantly
present according to menopausal status.
Tumour size is the most powerful predictor of breast
cancer for local recurrence, regional and systemic
Table I
The relationship of LVI with prognostic markers of breast
cancer
No of patients LVI (+)
(n = 81)
Pre 30 (37)* 17 (57)
Menopausal status p = 0.2491
Post 51 (63) 21 (41)
Positive 55 (68) 16 (29)
Oestrogen receptor p < 0.0001
Negative 26 (32) 22 (85)
Positive 51 (63) 16 (31)
Progesterone receptor
Negative 30 (27) 22 (73) p = 0.0004
Tumour size 0-2 cm 34 (42) 10 (29)
2-5 cm 41 (51) 22 (54) p = 0.028
> 5 cm 6 (7) 6 (100) p = 0.002
Nuclear grade 1 7 (9) 0
2 48 (51) 18 (38)
3 26 (32) 20 (77) p < 0.001
Axillary lymph node
Negative 36 (44) 5 (14)
Positive 45 (56) 33 (73) p < 0.0001
Positive 1-3 23 13 (57) p < 0.0001
Positive 4-9 15 13 (87) p < 0.0001
Positive > 10 7 7 (100) p < 0.0001
* Numbers in parentheses are percentages.
Table II
The rate of positive LVI according to markers
of poorer prognosis
Prognostic Markers Rate of positive LVI (%)
Grade 2 38
T2 54
Premenopausal 57
PR* negative 73
Axilla positive 73
Grade 3 77
OR* negative 85
Positive 4-9 nodes 87
T3 100
Positive > 10 nodes 100
Fatal metastatic disease 100
* OR : Oestrogen receptor, PR : Progesterone receptor.
286 G. Gurleyik et al.
spread, and therefore for overall survival. There is a sig-
nificant decrease in disease-free survival for patients
with tumours greater than T1 (6, 8). Our findings have
confirmed a higher rate of LVI (+) with greater tumour
size. The observation of a gradual increase of positive
LVI rate according to tumour size has supported the
power of LVI for the prediction of a worse outcome.
Another marker of aggressive behaviour of the
tumour is the nuclear grade, which independently affects
disease-free and overall survival (8). According to our
results, LVI can also be accepted as a predictor of an
aggressive tumour, in that the presence of LVI has
increased up to 73% when the nuclear grade has been
determined as 3, whereas there is no positive LVI in
nuclear grade 1 tumours in our patients. NERI et al. (9)
have also reported that the decision to apply adjuvant
therapy should consider the presence of LVI as an indi-
cator of high biological aggressiveness.
The larger studies with a longer follow-up have
demonstrated that patients with ER-positive tumours
have longer disease-free intervals than patients with ER-
negative tumours (7, 9). Although there was a small
number of patients in our study, all patients (except one ;
86%) who died from invasive breast cancer had both ER
and PR-negative tumours. We can comment that patients
with hormone receptor negative tumours have a poorer
prognosis ; therefore, LVI (+) can also confirm a worse
outcome. A significantly lower LVI (+) rate in ER and
PR positive tumours has supported the suggestion that
the presence of LVI affects the differentiation status of
the malignant cells.
Axillary lymph node involvement is accepted as the
most powerful marker of systemic disease and poorer
prognosis that six of our seven patients died during
follow-up had more than four involved nodes. Recent
papers have reported that LVI has been found to be a
significant predictor of serious axillary metastasis and
poorer prognosis (10, 11). The presence of LVI has been
significantly associated with both a shortened disease-
free interval and disease specific survival (12). When
evaluating the relationship of LVI with axillary status,
our findings
have supported the significance of LVI on
the axillary involvement, in that the rate of LVI (+) has
gradually increased with the number of involved lymph
nodes. Axillary status represents a metastatic (systemic
spreading) ability of primary breast malignancy. Our LVI
results have also supported the predictive power of LVI
concerning the potential of metastasis ; when axillary
involvement progresses from negative to more than
ten nodes, the rate of positive LVI increases from 14 to
100%. In recent studies, LVI was also found predictive
of axillary involvement (13-15). SCHOPPMANN et al. (16)
have reported that the determination of lymphatic micro-
vessel density and LVI predicted high metastatic potential
in breast cancer, and LVI was significantly associated
with a higher risk for developing lymph node metastasis.
Patients with negative axilla have a relatively better
prognosis, but a small number (14%) of patients with
positive LVI despite negative axilla possess a distinct
importance. LVI is an adverse prognostic factor for local
and distant relapse and disease-free and overall survival.
Node negative patients with LVI are candidates for adju-
vant therapy (6-8). We must take into account this group
for adjuvant treatment based on the increased risk of
aggressive behavior due to LVI. The Ludwig Breast
Cancer Study Group studied the prognostic significance
of LVI in a large number of patients. They found lower
disease-free and overall survival in patients with peritu-
moural LVI (3). WOO et al. (2) followed up 1258 patients
during 12 years for the significance of various factors in
predicting survival. They suggested that patients with 0
to 3 lymph nodes and positive LVI may be candidates
for aggressive adjuvant therapy. Positive LVI could like-
ly be regarded as the precursor of nodal involvement.
Adjuvant chemotheraphy is almost always recommend-
ed for large tumours and node positive cases, so the
addition of LVI would have little effect on treatment
recommendations. On the other hand, chemotherapy
may be beneficial for small node negative tumours with
positive LVI. LVI may be used for adjuvant treatment
decisions especially in node negative patients. This
hypothesis should be supported with additional studies.
Table III
Markers of prognosis in patients who died from metastatic disease
Age/Menopause Tumour size Axillary status Grade Hormone receptor LVI
(cm) metastatic/total Status
67 post 3 19/25 3 OR (-) PR (-)* +
48 pre 2 9/15 2 OR (+) PR (+) +
40 pre 2 2/26 2 OR (-) PR (-) +
40 pre 4 5/14 3 OR (-) PR (-) +
51 pre 4 34/34 3 OR (-) PR (-) +
65 post 3 9/19 3 OR (-) PR (-) +
45 pre 3 8/17 3 OR (-) PR (-) +
*OR : Oestrogen receptor, PR : Progesterone receptor.
LVI, Prognostic Marker for Breast Cancer 287
Despite the relatively small number of patients and
the short follow-up period, we conclude that a high rate
of positive LVI shows a close relationship with poor
prognostic markers in patients with invasive breast can-
cer. The presence of peritumoral LVI may be used as an
indicator of biologically aggressive behaviour, of
metastatic ability, and of a regional and systemic spread-
ing risk of primary malignancy.
Based on our findings we can comment that LVI has
a close relationship with studied essential prognostic
markers except menopausal status.
References
1. Clark G. M. Prognostic and predictive factors. In :HARRIS J. R.,
LIPPMAN M. E., MORROW M., OSBORNE C. K. (eds.). Disease of the
Breast 2
nd
ed. Philadelphia : Lippincott Williams & Wilkins,
2000 : 489-514.
2. WOO C. S., SILBERMAN H., NAKAMURA S. K., YE W., COLBURN W. ,
WAISMAN J. R., SILVERSTEIN M. J. Lymph node status combined
with lymphovascular invasion creates a more powerful tool for
predicting outcome in patients with invasive breast cancer. Am J
Surg, 2002, 184 : 337-340.
3. DAVIS B. W., GELBER R., GOLDHIRSCH A. et al. Prognostic signifi-
cance of peritumoural invasion in clinical trials of adjuvant thera-
py for breast cancer with axillary lymph node metastasis. Hum
Pathol, 1985, 16 : 1212-1218.
4. PAGE D. L., ANDERSON T. J. Miscellaneous features of carcinoma.
In : Diagnostic Histopathology of the Breast 4
th
ed. UK : Langman
Group, 1987 : 283-284.
5. MCCREADY D. R., CHAPMAN J. A., HANNA W. M. et al. Factors
affecting distant disease-free survival for primary invasive breast
cancer : use of a log-normal survival model. Ann Surg Oncol,
2000, 7 : 416-426.
6. JAGSI R., RAAD R. A., GOLDBERG S. et al. Locoregional recurrence
rates and prognostic factors for failure in node-negative patients
treated with mastectomy : implications for postmastectomy
radiation. Int J Radiat Oncol Biol Phys, 2005, 62 : 1035-1039.
7. TRUONG P. T., YONG C. M., ABNOUSI F. et al. Lymphovascular inva-
sion is associated with reduced locoregional control and survival
in women with node-negative breast cancer treated with mastec-
tomy and systemic therapy. J Am Coll Surg, 2005, 200 : 912-921.
8. KURU B., CAMLIBEL M., ALI GULCELIK M., ALAGOL H. Prognostic
factors affecting survival and disease-free survival in lymph node-
negative breast carcinomas. J Surg Oncol, 2003, 83 : 167-172.
9. N
ERI A., MARRELLI D., ROVIELLO F. et al. Prognostic value of extra-
capsular extension of axillary lymph node metastases in T1 to T3
breast cancer. Ann Surg Oncol, 2005, 12 : 246-253.
10. T
RUDEAU M. E., PRITCHARD K. I., CHAPMAN J. A. et al. Prognostic
factors affecting the natural history of node negative breast cancer.
Breast Cancer Res Treat, 2005, 89 : 35-45.
11. RIVERS A. K., GRIFFITH K. A., HUNT K. K. et al. Clinicopathologic
features associated with having four or more metastatic axillary
nodes in breast cancer patients with a positive sentinel lymph
node. Ann Surg Oncol, 2006, 13 : 36-44.
12. SHEN J., HUNT K. K., MIRZA N. Q. et al. Predictors of systemic
recurrence and disease-specific survival after ipsilateral breast
tumour recurrence. Cancer, 2005, 104 : 479-490.
13. TAN Y. Y., WU C. T., FAN Y. G. et al. Primary tumour characteris-
tics predict sentinel lymph node macrometastasis in breast cancer.
Breast J, 2005, 11 : 338-343.
14. CALLEJO I. P., BRITO J. A., BIWAR J. W. et al. Predictors of positive
axillary lymph nodes in breast cancer patients with metastatic
sentinel lymph node. Clin Transl Oncol, 2005, 7 : 18-22.
15. CAO Y. , PANER G. P., RAJAN P. B. Sentinel node status and tumour
characteristics : a study of 234 invasive breast carcinomas. Arch
Pathol Lab Med, 2005, 129 : 82-84.
16. SCHOPPMANN S. F., BAYER G., AUMAYR K. et al. Austrian Breast and
Colorectal Cancer Study Group. Prognostic value of lymphangio-
genesis and lymphovascular invasion in invasive breast cancer.
Ann Surg, 2004, 240 : 306-312.
Gunay Gurleyik
Eski Bagdat cad. 29/9
Altintepe 34840, Istanbul, Turkey
E-mail : ggurleyik@yahoo.com
... Another marker of aggressive behavior of the tumour is the histopathological grade, which independently affects disease-free and overall survival (Kuru et al, 2003). Gurleyik et al (2007) reported that of LVI increases with the grade of tumor. In our study, higher grade tumor was present in 80% of cases with LVI positive compared to 46.7% of patients with LVI negative. ...
... So there was more chance of lymphatic invasion in higher grade tumors but the correlation was statistically insignificant (p=0.058). Gurleyik et al (2007) reported significant correlation between ER/PR status and lymphatic vascular invasion. In our study we found 84.6% LVI positive patients belonged to poorer prognostic hormonal receptor status combination (ER-PR-HER2/neu-or ER-PR-HER2/neu+), 15.4% belonged to intermediate prognostic group (ER± PR± HER2/neu±) and no patients in good prognostic group (ER+ PR+ HER2/neu) (p=0.046). ...
Prognostic Correlation of Color Doppler Ultrasonography and Lymphangiogenesis in Breast Carcinoma
Article
Full-text available
  • Jan 2021
Tumor vascularity and lymphangiogenesis are two established prognostic parameters however detecting a proxy marker could help in prognosticating patients in an early stage. We tried to investigate color doppler and Lymphatic vessel immunohistochemical staining in breast cancer patients and correlate it with established prognostic markers in breast cancer. 30 patients were included in the study with the mean age of 44.40±10.37 years (range 30-65 years). In color doppler, high RI value significantly correlated with T3 tumor size, number of lymph nodes (>10), grade (grade III), hormonal status, LMVD (high) and LVI D2- 40 positivity with a p-value of 0.0004, 0.001, 0.007, 0.006, 0.008 and 0.008 respectively. On correlation with PI, number of lymph nodes (>10), grade (grade III), hormonal status and LVI D2-40 positivity were significantly correlated with high PI value (p=0.044, p=0.012, p=0.013 and p=0.046 respectively). In Lymphatic vessel immunohistochemical staining high LMVD value significantly correlated with tumor size, number of lymph nodes, tumor grade and hormonal status (p=0.002, p=0.001, p=0.0006 and p=0.015) while LVI significantly correlated with tumor size, number of lymph nodes and hormonal status prognostic factors (p=0.008, p=0.013 and p=0.046 respectively).
View
... There was a considerable difference in LDH between the two groups, with the median LDH being highest in the group with positive lymphovascular invasion (LVI). Gurleyik et al., considered that cancer cells present within a specific endothelial-lined area (either lymphatic vessels or blood vessels) in the breast are definitive of lymphovascular invasion [31]. LVI has been linked in certain studies to a higher risk of axillary nodal metastases, distant metastases, and death. ...
Significance of Serum Lactate Dehydrogenase as a Prognostic Marker and Outcome Predictor in Patients With Breast Cancer
Article
Full-text available
  • Mar 2024
Background Breast carcinoma has been the most prevalent cancer in women, with research-based evidence showing a significant rise in the incidence of cancer and related morbidity and mortality in the Indian subcontinent. The predictive value of plasmatic lactate dehydrogenase (LDH) levels has been studied in breast cancer. Numerous studies have connected high LDH values to a poor prognosis, increased risk of incidence, recurrence, and associated mortality in patients with breast carcinoma. This study aimed to assess the clinical profile of breast carcinoma and determine the correlation of serum lactate dehydrogenase levels with the stage of the disease and assessment of high-risk features using histopathology and immunohistochemistry. Methods A total of 75 patients with carcinoma breast were enrolled for this study and classified into two groups: upfront surgery and post-adjuvant therapy. Serum LDH levels were estimated a day before the surgery (baseline) and on postoperative days 1, 7, 14, and 30. The clinical tumor, node, metastasis (cTNM) staging was correlated with pathological tumor, node, metastasis TNM (pTNM) staging and immunohistochemistry findings. Results The clinical characteristics of breast cancer, serum LDH levels, and stage of the disease were collected and analyzed. A significant decreasing trend was noted in LDH values post-op days, and statistically significant higher LDH values were noted in the triple-negative group, positive lymph nodes, and positive lymphovascular invasion patients. Conclusion Regularly elevated levels or an unanticipated rise in serum LDH might indicate poor outcomes. Hence, this non-specific enzyme marker can be suggested to be used routinely to assess disease outcomes.
View
... In a study by Rezaianzadeh et al (22), the prognostic role of LVI was notably associated with involvement of axillary lymph nodes. LVI has been frequently shown to be a predictor of lymph node metastasis in many studies (22) (23,24). In multivariate analysis, LVI was consistently the most significant variable associated with nodal disease with an OR of 6.62 at 95% CI. ...
Histopathological indicators of lymph node positivity in breast cancer patients: A Retrospective analysis
Article
Full-text available
  • Jun 2023
Objective: Since axillary lymph node involvement is the main cause of breast cancer surgical morbidity, identifying lymph node metastasis predictions might improve clinical outcomes. To predict the association of axillary lymph node positivity with involvement in breast cancer by using histopathological indicators. subtype were acquired from histopathological reports. The association between tumour features and lymph node status was assessed. Results: Age at diagnosis, lymphovascular invasion, Her2/neu status, and Her2/neu-enriched molecular subtype were significantly associated (p<0.05) with lymph node positive. Nodal metastases [54% (27/50)] and high Ki67 index [24% (12/50)] associated with lymph node positivity in total number of patients. Conclusion: This study predicted breast cancer axillary lymph node involvement using lympho-vascular invasion, age at diagnosis, Her2/neu status, Her2/neu-enriched molecular subtype, and Ki67 index. This data may be utilized for breast cancer diagnosis and treatment.
View
... It is known that despite a generally favorable prognosis for primary operable breast cancer, in cases of high malignancy or HER2 overexpression, survival rates decrease to 70-75% [35]. The invasion of the lymphatic vessels around the tumor significantly correlates with the size of the primary lesion, the histological malignancy of breast cancer, the involvement of the axillary lymph nodes, and the expression of hormone receptors [36]. The type of treatment was determined by the tumor's corresponding clinical and pathological characteristics; therefore, it naturally affected the prognosis of breast cancer. ...
Prognostic Value of Salivary Biochemical Indicators in Primary Resectable Breast Cancer
Article
Full-text available
  • Jun 2022
Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and the risk of recurrence of primary resectable breast cancer. The study included 355 patients of the Omsk Clinical Oncology Center with a diagnosis of primary resectable breast cancer (T1-3N0-1M0). Saliva was analyzed for 42 biochemical indicators before the start of treatment. We have identified two biochemical indicators of saliva that can act as prognostic markers: alkaline phosphatase (ALP) and diene conjugates (DC). Favorable prognostic factors were ALP activity above 71.7 U/L and DC level above 3.93 c.u. Additional accounting for aspartate aminotransferase (AST) activity allows for forming a group with a favorable prognosis, for which the relative risk is reduced by more than 11 times (HR = 11.49, 95% CI 1.43–88.99, p = 0.01591). Salivary AST activity has no independent prognostic value. Multivariate analysis showed that tumor size, lymph nodes metastasis status, malignancy grade, tumor HER2 status, and salivary ALP activity were independent predictors. It was shown that the risk of recurrence decreased with menopause and increased with an increase in the size of the primary tumor and lymph node involvement. Significant risk factors for recurrence were salivary ALP activity below 71.7 U/L and DC levels below 3.93 c.u. before treatment. Thus, the assessment of biochemical indicators of saliva before treatment can provide prognostic information comparable in importance to the clinicopathological characteristics of the tumor and can be used to identify a risk group for recurrence in primary resectable breast cancer.
View
... Our cohort study involved 130 BC patients with mean of age was 53.13 years old. Median age of breast cancer patients in Asia was similar with our findings as shown by studies Turkey (Gurleyik et al., 2007), Thailand (Chuthapisith et al., 2012) and China (Zhao et al., 2012) as well as from Brazil (Marinho et al., 2008). In Caucasian, age at breast cancer diagnosis is generally older (> 60 years-old) as shown by studies from Miami (El-Gohary et al., 2008) and Winconsin (Onitilo et al., 2009). ...
Prognostic Value of Lymphangiogenesis Determinants in Luminal and Non-luminal Breast Carcinomas
Article
Full-text available
  • Sep 2018
Background: Breast carcinomas (BCs) are sub-classified according to the molecular characteristics into luminal and non-luminal subtypes that clinically show different biological behavior, treatment and prognosis. BCs spread primarily through lymphatic vessels using cascade processes of lymphagiogenesis in which VEGF-C plays an important role during lymph node metastasis. Prognostic value of VEGF-C in luminal and non-luminal BC is still unclear and has not been studied thoroughly to clarify and define prognosis and therapeutic monitoring. Aim: To define the prognostic value of lymphangiogenesis on survival rates of luminal and non-luminal subtypes BC. Materials and Methods: This study applied prospective cohort design, using 130 patients of invasive duct carcinoma of the breast, stage I-IIIA, from Sardjito General Hospital, Indonesia and subsequent longitudinal follow-up. Immunohistochemical staining was carried out using anti-ER, -PR, -Her-2, VEGF-C, VEGFR-3 and D2-40 antibodies. The related clinicopathologic characteristics of BC patients and lymphangiogenesis determinants, including VEGF-C expression, were statistically analyzed. Results: In non-luminal BC subtypes, VEGF-C expression (HR=0.04; 95% CI=0.01-0.41), lymph node metastasis (HR=0.14; 95% CI=0.04-0.55) and stage (HR=0.30; 95% CI= 0.02-0.76) were determined as independent prognostic factors on survival rates. However, the lymphangiogenesis determinants were not associated with the survival rates of luminal BC subtypes. Conclusion: This study suggested that lymphangiogenesis affects survival rates of non-Luminal subtype rather than the luminal subtypes of BC.
View
Lymphovascular Invasion and Ductal In-situ Components in Operable Infiltrating Duct Carcinoma of BreastA Single Centre Experience
Article
Full-text available
  • Aug 2022
Introduction: Lymphovascular Invasion (LVI) in carcinoma breast is a significant prognostic factor in invasive breast cancer, with respect to local and distant recurrence and poor survival. Infiltrating duct carcinoma with accompanying ductal carcinoma in-situ has shown significantly different expression patterns of Her2/neu, progesterone receptors and Ki67 than infiltrating duct carcinoma. Aim: To associate the significance of LVI and concomitant insitu component with the receptor status and clinicopathological characteristics of infiltrative duct carcinoma. Materials and Methods: This retrospective study was conducted in a single unit in the Department Of General Surgery, Government Medical College, Thrissur, Kerala, India, for two months between June 2021 and July 2021 and data was analysed in August 2021. This study was conducted in a systematic manner to review all the operated infiltrative duct carcinoma patients from a single cohort in 100 patients based on surgical intervention. The collected data were entered in Microsoft Excel worksheet and the results were analysed statistically using Statistical Package of the Social Sciences (SPSS)-16. Chi-square test was used, considering p-value ≤0.05 as a significant. Results: The mean age of the study population was 55.6±15 years with maximum number of patients above 60 years. In total 64% of the patients had tumour size of 2-5 cm (pT2) and 59% of the cases had no lymph nodal metastasis (pN0). 28 cases (28%) showed concomitant in-situ component and 37 cases showed lymphovascular invasion (37%). The presence of lymphovascular invasion, was found to be significantly associated with Her2 positivity (p=0.045). Concomitant in-situ component also seemed to increase the likelihood of lymphovascular invasion (p=0.0320). There was significant positive correlation observed between LVI and Her2 (r=0.238, p=0.045) and in-situ component (0.214; p=0.032). However, no significant association was observed between LVI and other clinicopathological variables. Conclusion: The LVI is a significant prognostic factor in invasive breast cancer associated with poor survival and definitely carries a significant association with Her2 Status and also reflected on the concomitant in-situ carcinoma.
View
Hubungan Antara Ukuran Tumor dan Gradasi Histopatologi dengan Metastasis Kelenjar Getah Bening pada Penderita Kanker Payudara di RSUD Al-Ihsan Provinsi Jawa Barat
Article
  • Jan 2022
Breast cancer is a malignancy that occurs in the epithelial tissue of the lobules or ducts of the breast glands. The majority of breast cancer patients come in an advanced stage, which impacts the patient's prognosis. The prognosis of breast cancer can be seen from various prognostic factors. This study aimed to analyze the relationship between tumor size and histopathological gradation with lymph node metastases in breast cancer patients. This cross-sectional study was conducted at Al-Ihsan Hospital, West Java Province on 76 patients. Data obtained from medical records in the form of histopathology lab results taken from January 2020 - December 2020. The data used univariate and bivariate tests. The results of the univariate statistical test showed that the characteristics of breast cancer patients were mostly T3 tumors, histopathological grade 3, and lymph node metastases were negative. The bivariate analysis results showed no relationship between tumor size (P=0.051) and histopathological gradation (P=0.912) with lymph node metastases. Abstrak. Kanker payudara merupakan keganasan yang terjadi pada jaringan epitel lobulus atau duktus dari kelenjar payudara. Mayoritas pasien kanker payudara datang dalam stadium lanjut yang memberikan dampak pada prognosis penderita. Prognosis kanker payudara dapat dilihat dari berbagai faktor prognostik. Tujuan penelitian ini untuk menganalisis hubungan antara ukuran tumor dan gradasi histopatologi dengan metastasis kelenjar getah bening pada penderita kanker payudara. Penelitian cross sectional ini dilakukan di RSUD Al-Ihsan Provinsi Jawa Barat pada 76 pasien. Data diperoleh dari medical record berupa hasil lab histopatologi yang diambil dari Januari 2020 – Desember 2020. Data menggunakan uji univariat dan bivariat Hasil uji statistik univariat didapatkan karakteristik pasien kanker payudara mayoritas berukuran tumor T3, berderajat histopatologi 3, dan metastasis kelenjar getah bening negatif. Hasil analisis bivariat didapatkan tidak terdapat hubungan antara ukuran tumor (P=0,051), dan gradasi histopatologi (P=0,912) dengan metastasis kelenjar getah bening.
View
A retrospective review of MRI features associated with metastasis-free survival in women with breast cancer: focusing on skin thickening and skin enhancement
Article
  • Sep 2021
Objectives To identify associations between MRI-detected skin thickening and enhancement and metastasis-free-survival (MFS) given recent reports of skin thickening on ultrasound being a poorer prognostic indicator. Methods Interrogation of a prospectively collected database of ultrasound-visible breast lesions showed 214 lesions with pre-treatment MRIs available for analysis in a single centre. Data on metastasis-free-survival (MFS) was prospectively collected. Retrospective MRI review was performed blinded to outcome. Imaging factors recorded were presence of skin thickening and enhancement, non-mass-enhancement (NME) and abnormal nodes, mass characteristics, perilesional oedema and background parenchymal enhancement. Statistical analysis used Chi-squared test, Kaplan-Meier survival curves, the Log-rank test and Receiver-Operator-Characteristic (ROC) curves. Results During a median follow-up period of 5.6 years, 21 (10%) of 212 patients developed distant metastases. Skin thickening [24 of 30 (80%) vs 169 of 184 (92%), p = 0.043] and skin enhancement [15 of 20 (75%) vs 178 of 194 (92%), p = 0.016] were associated with poorer MFS. Large index lesion size [p < 0.001, AUC 0.823], large sum of masses [p < 0.001, AUC 0.813], increasing total lesion extent including NME [p < 0.001, AUC 0.749] and abnormal axillary nodes [55 of 66 (83%) vs 138 of 148 (93%), p = 0.024] were also associated with poorer MFS. Conclusions Skin thickening and enhancement on breast MRI are associated with poorer MFS. These findings should be taken into account when managing patients with invasive breast cancer. Advances in knowledge Skin enhancement on breast MRI at diagnosis is associated with metastases development. Skin thickening on breast MRI is associated with future metastatic disease.
View
Podoplanin Expression in Cancerous Stroma Induces Lymphangiogenesis and Predicts Lymphatic Spread and Patient Survival
Article
  • Oct 2010
Context.—Podoplanin is a mucin-type glycoprotein and a lymphatic endothelial marker. Immunohistochemical staining for podoplanin is currently used as a routine pathologic diagnosis tool in Japan to identify lymphatic invasion of cancer cells. Recent reports suggest that podoplanin and other proangiogenic molecules are expressed in stromal fibroblasts and myofibroblasts. Objective.—To analyze the distribution of podoplanin expression in tumor stroma and its clinical and biologic significance. Design.—We performed immunohistochemistry for podoplanin on tissue microarrays from 1350 cases of 14 common cancer types. Results.—Two hundred eighty-seven of 662 cases (43%) showed podoplanin expression in the stromal cells within cancer nests. Stromal podoplanin expression in 14 common cancer types was significantly associated with tumor stage (P < .001), lymph node metastases (P < .001), lymphatic invasion (P = .02), and venous invasion (P < .001). The stromal cells positive for podoplanin were also positive for α-smooth muscle actin but negative for desmin, confirming a myofibroblasts phenotype. In contrast, myofibroblasts in inflammatory fibrotic lung diseases were podoplanin negative. Lymphatic vessel density was greater in the stromas with podoplanin expression than in the stroma lacking podoplanin-expressing stromal cells (P = .01). Survival data were available for non–small cell lung cancer. Stromal podoplanin expression was associated with poorer prognosis in adenocarcinoma (P < .001) and remains statistically significant after adjustment for sex, age, and stage (P = .01). Conclusion.—Our data indicate that podoplanin expression in stromal myofibroblasts may function as a proangiogenic biomarker and may serve as a predictive marker of lymphatic/vascular spread of cancer cells and a prognostic marker of patient survival.
View
Faktor yang Berpengaruh Terhadap Disease Free Survival dan Overall Survival pada Pasien Kanker Payudara Usia Muda di Kota Padang Tahun 2008 - 2018
Article
Full-text available
  • Jan 2020
Kanker Payudara (KPD) pada usia muda memiliki keistimewaan karakteristik. Rekurensi KPD dipengaruhi oleh berbagai faktor antara lain faktor klinis, regimen terapi dan biomolekuler dari tumor itu sendiri. Berbagai macam modalitas terapi KPD, namun masih terdapat risiko terjadinya rekurensi terutama pada pasien dewasa muda. Tujuan: Mengetahui faktor-faktor yang mempengaruhi Disease Free Survival (DFS) dan Overall Survival (OS) pada pasien KPD usia muda di Kota Padang. Metode: Penelitian ini menggunakan desain cohort study retrospectif pada pasien KPD usia muda yang telah mendapatkan pengobatan KPD yang memenuhi kriteria inklusi sebanyak 103 sample yang terdapat pada data register KPD PERABOI Padang. Analisis survival menggunakan Kaplan Meier dengan Log Rank Test. Apabila diperoleh nilai p < 0,05, maka terdapat hubungan bermakna. Hasil: Terdapat perbedaan antara setiap faktor klinis, faktor biomolekuler dan faktor terapi dalam hal rata-rata DFS maupun rata-rata OS, namun tidak terdapat pengaruh yang bermakna secara analisis statistik antara faktor terapi (terapi hormon, radioterapi dan terapi target) terhadap DFS dan OS pada pasien kanker payudara usia muda di Kota Padang (p>0,05). Terdapat pengaruh dari pemberian kemoterapi terhadap DFS pada pasien kanker payudara usia muda di Kota Padang (p<0,05). Simpulan: Tidak terdapat hubungan yang bermakna antara faktor klinis dan faktor biomolekuler dengan DFS dan OS, namun terdapat hubungan bermakna antara pemberian kemoterapi dengan DFS dan OS pada penderita KPD usia muda di kota Padang tahun 2008 – 2018.
View
Factors Affecting Distant Disease-Free Survival for Primary Invasive Breast Cancer: Use of a Log-Normal Survival Model
Article
Full-text available
  • Apr 2012
Background: Invasive breast cancer is a frequently diagnosed disease that now comes with an ever expanding array of therapeutic management options. We assessed the effects of 20 prognostic factors in a multivariate context. Methods: We accrued clinical data for 156 consecutive patients with stage 1–3 primary invasive breast cancer who were diagnosed in 1989–1990 at the Henrietta Banting Breast Center, and followed to 1995. There is complete follow-up for 91% of patients (median follow-up of 4.9 years). The event of interest was distant recurrence (for distant disease-free survival, DFS). We used Cox and log-normal step-wise regression to assess the multivariate effects of the following factors on DFS: age, tumor size, nodal status, histology, tumor and nuclear grade, lymphovascular and perineural invasion (LVPI), ductal carcinoma-in-situ (DCIS) type, DCIS extent, DCIS at edge of tumor, ER and PgR, ERICA, adjuvant systemic therapy, ki67, S-phase, DNA index, neu oncogene, and pRb. Results: There was strong evidence against the Cox assumption of proportional hazards for nodal status, and nodal status was not in the Cox step-wise model. With step-wise log-normal regression, a large tumor size (P < .001), positive nodes (P 5 .002), high nuclear grade (P 5 .01), presence of LVPI (P 5 .03), and infiltrating duct carcinoma not otherwise specified (P 5 .05) were associated with a reduction in DFS. Conclusions: For nodal status, there was strong evidence against the Cox assumption of proportional hazards, and it was not included in the Cox model although it was in the log-normal model. Only traditional factors were included in the step-wise models. Thus, this statistical management of prognostic markers in breast cancer appears to be very important.
View
Prognostic value of extracapsular extension of axillary lymph node metastases in T1 to T3 breast cancer
Article
Full-text available
  • Mar 2005
The importance of extracapsular extension (ECE) of axillary metastases as a risk factor for either local or distant recurrence and poorer survival in breast cancer has been suggested, but its prognostic value has not been uniformly confirmed. From a prospective database including 1142 breast cancer patients operated on at the Department of General Surgery and Surgical Oncology of the University of Siena, we selected 376 cases with pT1 to pT3 node-positive breast cancer. The prognostic significance of ECE of axillary metastases was evaluated with respect to disease-free survival, overall survival, and the patterns of disease recurrence. Such prognostic significance was then compared with that of other clinical and pathologic factors. With a median follow-up of 103 months, factors with independent prognostic value for disease-free survival by multivariate analysis included absence of estrogen receptors (P < .0005), pN category (P < .01), presence of lymphovascular invasion (LVI; P < .005), and ECE (P < .0001). An independent negative prognostic effect on overall survival was observed for absence of estrogen and progesterone receptors (P < .05), pN category (P < .05), and presence of LVI (P < .005) and ECE (P < .0001). The presence of ECE was significantly related to an increased risk of regional (13.4% vs. 6.6%; P = .037) and distant (43% vs. 16.2%; P < .001) recurrences. ECE demonstrated a stronger statistical significance in predicting prognosis than the pN category and was also related to an increased risk of distant recurrences. We suggest that the decision on adjuvant therapy should consider the presence of ECE of axillary metastases and peritumoral LVI as indicators of high biological aggressiveness.
View
View
View
Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis
Article
  • Jan 1986
  • Hum Pathol
To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.
View
Lymph node status combined with lymphovascular invasion creates a more powerful tool for predicting outcome in patients with invasive breast cancer
Article
  • Nov 2002
  • AM J SURG
Multiple clinical, biologic, and pathologic factors are known to correlate with outcome in patients with invasive breast cancer. The utility of lymphovascular invasion as an additional useful prognostic indicator has been heretofore ill defined. The purpose of the current study was to determine whether the presence or absence of peritumoral lymphovascular invasion (LVI) contribute further significant information in assessing survival. Using a prospective database of 1,258 patients with invasive breast cancer followed up for as long as 12 years, eight factors were evaluated for their impact on patient survival: lymph node status, LVI, age at diagnosis, tumor size, tumor palpability, estrogen and progesterone receptor status, and nuclear grade. Multivariate analysis revealed that both lymph node status and the presence or absence of LVI were highly significant independent predictors of outcome. Knowledge of both lymph node status and the presence or absence of LVI can be used to predict which subset of patients will do extremely well (node negative + LVI absent) or extremely poorly (node positive + LVI present). The combination of the two factors is most meaningful in patients with 1 to 3 positive nodes.
View
Prognostic factors affecting survival and disease free survival in lymph node negative breast carcinoma
Article
  • Jul 2003
The objective of this study was to identify the patients who are at low or high-risk by defining the prognostic factors in node-negative breast carcinomas. Medical records of 384 consecutive breast cancer patients with negative axillary lymph nodes who had been operated on between January 1994 and January 1997 at our hospital were retrospectively reviewed. Several clinical and pathological characteristics of patients were categorized. Univariate analyses of survival and disease-free survival (DFS) were performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting survival and DFS were assessed by Cox proportional hazard method. 5-year survival and DFS were 91.4 and 85.7%, respectively. Size, grade, age, and lymphovascular invasion (LVI) were the prognostic factors that independently affected survival and DFS. Tamoxifen improved survival and DFS. While age younger than 35 was an adverse factor for both survival and DFS, age older than 49 was a detrimental factor for DFS. Patients who have a tumor with size greater than 2 cm, with histologic grade 3, with LVI, and patients with age under 35 or older than 49 have poorer prognosis among node-negative breast carcinomas, and are candidates for adjuvant therapy.
View
Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast Cancer
Article
  • Sep 2004
The aim of this study was to investigate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in a large cohort of breast cancer patients. Invasion of tumor cells into blood and lymphatic vessels is one of the critical steps for metastasis. The presence or absence of lymph node metastasis is one of the main decision criteria for further therapy. One shortcoming of previous morphologic studies was the lack of specific markers that could exact discriminate between blood and lymphatic vessels. The aim of this study was to evaluate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in breast cancer patients. We investigated 374 tissue specimens of patients suffering from invasive breast cancer by immunostaining for the lymphatic endothelial specific marker podoplanin. Lymphangiogenesis, quantified by evaluating the lymphatic microvessels density (LMVD), and lymphovascular invasion (LVI) were correlated with various clinical parameters and prognostic relevance. LMVD correlated significantly with LVI (P = 0.001). LVI was associated significantly with a higher risk for developing lymph-node metastasis (P = 0.004). Calculating the prognostic relevance, LVI presented as an independent prognostic parameter for disease free as well as overall survival (P = 0.001, and P = 0.001, respectively). Our data provide evidence that the biologic system of lymphangiogenesis constitutes a potential new target for development of anti-breast cancer therapeutic concepts. Our results further suggest that young, premenopausal patients with low differentiated breast tumors and high LMVD and LVI would, in particular, benefit from lymphangiogenesis-associated therapeutic strategies.
View
Sentinel node status and tumor characteristics: A study of 234 invasive breast carcinomas
Article
  • Jan 2005
  • ARCH PATHOL LAB MED
Axillary lymph node status is the most important prognostic factor in patients with breast cancer. Tumor size and lymph node status, the most reliable pathologic bases of the tumor staging system, are practical parameters for estimating survival status. With the advent of lymphatic mapping and sentinel node (SN) identification, there is potential for a more efficient and sensitive evaluation of the axillary lymph node status. To correlate SN status with tumor size, grade, and lymphovascular invasion. We examined 234 patients with unifocal breast carcinomas measuring 25 mm or less as detected by preoperative ultrasound during the period May 1998 through December 2002. Sentinel nodes were examined by frozen section and paraffin section as per protocol. Of the 234 patients, SN was identified in 221 (94.5%). An average of 1.38 SNs were examined per patient. Seventy-seven of 221 patients were SN positive on paraffin section. Sixty-six (85.7%) of these 77 cases could be correctly diagnosed as positive for metastatic carcinoma on frozen section. Two cases reported as positive on paraffin section were reported as suspicious on frozen section. Logistic regression indicated that tumor size, grade, and lymphovascular invasion were all significantly associated with SN status (P < .001). Tumor size, grade, and lymphovascular invasion were significantly associated with SN status in unifocal invasive breast carcinoma.
View
Prognostic factors affecting the natural history of node-negative breast cancer
Article
  • Feb 2005
We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer. The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast. Paraffin-embedded tumour tissue was available for the majority of patients. The following factors were examined for their univariate and multivariate effects on time to recurrence outside the breast (DFI) and survival from breast cancer (DSS): age, weight, tumour size, estrogen receptor, progesterone receptor, histologic type, tumour grade, nuclear grade, lymphovascular invasion, overexpression of neu oncoprotein, DNA ploidy, % cells in S-phase, and adjuvant therapy. Multivariate analyses utilized a Cox model with a step-wise factor selection for the 260 patients with complete information. A worse prognosis was indicated when there was lymphovascular invasion (for DFI, p < 0.001; for DSS, p = 0.0046), high %S-phase (for DFI, p = 0.08; for DSS, p = 0.02), high tumour grade (for DFI, p = 0.02; for DSS, p = 0.03), and overexpression of neu oncoprotein (for DSS, p = 0.07). In our natural history investigation, two factors, lymphovascular invasion and tumour grade, are of particular interest since they may be readily incorporated into clinical practice. Overexpression of neu oncoprotein may also play a role in determining prognosis for women administered adjuvant systemic therapy.
View