help button home button The Oncologist
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
The Oncologist, Vol. 12, No. 6, 636-643, June 2007; doi:10.1634/theoncologist.12-6-636
© 2007 AlphaMed Press

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tacca, O.
Right arrow Articles by Chollet, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tacca, O.
Right arrow Articles by Chollet, P.

Breast Cancer

Changes in and Prognostic Value of Hormone Receptor Status in a Series of Operable Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Olivier Taccaa,b, Frédérique Penault-Llorcaa,c, Catherine Abriala,b, Marie-Ange Mouret-Reyniera, Inès Raoelfilsa, Xavier Durandoa,b, Jean-Louis Acharda, Pierre Gimberguesa, Hervé Curéb,e, Philippe Cholleta,d

aCentre Jean Perrin, Clermont-Ferrand, France; bINSERM U484, Clermont-Ferrand, France; cUniversité d'Auvergne, Clermont-Ferrand, France; dCentre d'Investigation Clinique, Clermont-Ferrand, France; eInstitut Jean Godinot, Reims, France

Key Words. Hormone receptor status • Neoadjuvant chemotherapy • Breast cancer • Allred score

Correspondence: Olivier Tacca, Ph.D., Bureau de Recherche Clinique, Centre Jean Perrin 58, rue Montalembert, BP 392, 63011 Clermont-Ferrand Cedex 1, France. Telephone: 33-473278005; Fax: 33-473278029; e-mail: recherche.clinique{at}cjp.fr

Received December 5, 2006; accepted for publication April 9, 2007.


   ABSTRACT
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Disclosure of Potential...
 References
 
The aim of this study was to detect and analyze changes in hormone receptor (HR) status after treatment of operable breast cancer with neoadjuvant chemotherapy (NCT). Patients were treated from 1982 to 2004 with different NCT combinations, mainly in successive prospective phase II trials. HR status before and after NCT was retested and reviewed in a blinded fashion by two pathologists, for 420 patients from a database of 710 patients. Among these 420 tumors, 145 (35%) were HR negative and 275 (65%) were HR positive before NCT. The HR status had changed after treatment in 98 patients (23%): 61 patients (42%) initially HR negative became HR positive. This HR-positive switch was significantly correlated with better overall survival (OS), compared with patients with unchanged HR-negative tumors. Moreover, this HR-positive switch also had an effect on disease-free survival (DFS). Conversely, 37 patients (13%) initially HR positive became HR negative after NCT. However, this group of previously positive patients still had a survival advantage for OS, but not for DFS. The Allred score was evaluated before and after chemotherapy. An increase in Allred score after NCT was significantly correlated with better DFS but not OS. It was previously shown, for other tumor parameters, that residual disease after NCT, rather than parameters evaluated on the initial biopsy, must be considered for patient prognosis. In this work, NCT induced variations in HR status in 23% of patients. A positive switch in HR status after NCT could be an indicator of better prognosis for patient outcome.

Disclosure of potential conflicts of interest is found at the end of this article.


   INTRODUCTION
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 Conclusion
 Disclosure of Potential...
 References
 
Neoadjuvant chemotherapy (NCT) was initially used to treat inflammatory and locally advanced breast carcinoma and to improve local control, and if possible patient survival. More recently, this strategy has been extended to the management of patients with operable disease, eligible for mastectomy, mainly in order to increase the rate of breast conservation [1].

Nowadays, it is established that positive hormone receptor (HR) status acts as a favorable prognostic factor, and also as a strong predictor of response to adjuvant hormonal therapy. However, in contrast to stable parameters such as human epidermal growth factor receptor (HER)-2 status [2, 3], modifications in HR status have been described in the literature. Aromatase levels and progesterone receptor (PgR) levels have been shown to be modified in residual disease after induction chemotherapy in breast cancer treated by NCT (docetaxel) [4]. Arpino et al. [5] have shown that HR status of contralateral breast cancer is independent of the receptor status of the first primary in the absence of adjuvant tamoxifen. Moreover, Lower et al. [6], in a retrospective study, found a discordant HR status in 30% of cases between the primary and metastatic tumors from the same individual. This discordance in HR status had an impact on the overall survival (OS) of these patients. Nicolini et al. [7] found, in 10%–30% of cases, a conversion rate from estrogen receptor (ER)+ to ER– and from ER– to ER+ between the primary tumor and the metastatic relapse.

The purpose of this study was to investigate the concordance rate of HR status between the initial biopsy and the tumor remaining after NCT.


   PATIENTS AND METHODS
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 Conclusion
 Disclosure of Potential...
 References
 
Patient Population
In the present study, we analyzed the HR status of 420 patients out of 710 who received NCT for operable bulky breast cancer. Patients with primary inflammatory carcinoma were excluded. The majority of these patients had been treated at our institution (Centre Jean Perrin, Clermont-Ferrand) and the others were treated at the Centre Hospitalier Universitaire (Tours), Centre Paul Papin (Angers), and Centre Hospitalier (Brive-la-Gaillarde). The baseline workup included clinical examination, bilateral mammography, and bilateral breast ultrasound. The diagnosis of carcinoma was established through fine-needle aspiration or needle core biopsy of the primary tumor and palpable lymph nodes. When invasive adenocarcinoma was demonstrated, the tumor was evaluated for Scarff-Bloom-Richardson (SBR) grading. Table 1 shows the main clinicopathological characteristics of the patients included in this study.


View this table:
[in this window]
[in a new window]

  		Table 1. Patient and tumor characteristics according to type of neoadjuvant chemotherapy

 
The absence of distant metastasis was confirmed by chest x-ray, bone scan, and liver ultrasound. HR status was re-evaluated, before and after NCT, for 420 tumors among the 710 tumors in the database already published [8]. We could not retest 290 tumors for several reasons, ranging from an absence of available biopsy before NCT, a lack of informative remaining material on biopsy, patients who had a pathological complete response, or an insufficient number of remaining tumor cells after NCT to assess receptor status in paired samples.

Treatment Modalities
NCT in these 710 patients with operable breast cancer has already been summarized in detail from prospective phase II clinical trials; for most patients treatment was with one of the following five protocols: AVCF (doxorubicin, vincristine, cyclophosphamide, fluorouracil), NEM (vinorelbine, epirubicin, methotrexate), Taxobel (docetaxel), TNCF (theprubicin, vinorelbine, cyclophosphamide, fluorouracil), and FEC (fluorouracil, epirubicin, cyclophosphamide) [9–13]. Changes in pathological prognostic factors have been described for the whole series in two papers [10, 14]. Patients received a median number of six cycles of NCT (range, 1–9). Chemotherapy was administrated i.v. at 21- or 28-day intervals. After treatment, patients underwent appropriate surgery according to the size of their residual tumor.

From this series, 54 patients did not undergo surgery: 44 were treated with radiotherapy alone and 10 were withdrawn from the study because of progression, acute allergies, or surgery refusal after clinical complete response, and were treated with additional chemotherapy. As shown in Table 1, 656 patients were operated on after six cycles of treatment: surgery was conservative for 470 patients (66%) and 44 of them received radiotherapy alone, allowing a 73% breast conservation rate. Modified radical mastectomy was used for low responders (n = 186, 26%).

Determination of HR Status
Two tumor samples were compared when available for the analysis of HR status of the tumor. The first biopsy was a needle core performed before NCT. The second came from the remaining tumor at surgery. A centralized comparative evaluation of ER and PgR status was realized by immunohistochemistry (IHC). To ensure homogeneity of the HR results, HR status was retested on a new section for all patients. The Novocastra antibodies 6F11 (1/40th) and PgR636 (1/30th) (Novocastra Laboratories Ltd., Newcastle, UK) were used for the detection of ER and PgR, respectively, using a Ventana NeXes automat (Ventana Medicals Systems, Illkirch, France). The revelation was performed with the AEC detection kit from Ventana Medicals Systems.

HR status was then reevaluated in a blinded fashion by two pathologists, on 420 patients.

Scoring System for HR Status
The HR status was considered as positive if either the ER or PgR status, or both, were positive. The HR status was considered negative when both the ER and PgR status were negative. We used two scoring systems.

The 10% cutoff system is currently used and recommended in France. The cutoff value for positivity was 10% of invasive tumor cells with stained nuclei.

Allred Score
The Allred score is a quantitative evolution of positivity of HR status by IHC [15]. We performed this test to evaluate the potential magnitude of HR change. It was calculated in two steps. First, a proportion score was determined, which represented the estimated proportion of positive-staining tumor cells (0, negative; 1, 0 to <1%; 2, 1%–10%; 3, 10%–33%; 4, 33%–66%; 5, >66%). A second score was determined and represented the average intensity of positive tumor cells (0, none; 1, weak intensity; 2, intermediate; 3, strong). The Allred score was obtained by the addition of the proportion score to the intensity score. This score ranged from 0–8 and determined the tumor's positivity [15]. An Allred score >2 was used to define tumor ER positivity.

Reproducibility
Our pathology lab is involved in quality assurance procedures in breast cancer on a daily basis with the use of proper controls including low-intensity cases. The laboratory participates in external quality assurance tests for ER and PgR every year (AFAQAP).

In this study, we separately analyzed 100 patients (control group) who did not receive NCT between biopsy and surgical procedure. In this control group, three patients (3%) had a discordant HR status between biopsy and surgical specimen.

Statistical Analysis
All response rates are presented with their 95% confidence intervals (CIs). Relations between all parameters studied and the diagnosis periods were evaluated using {chi}2 tests. p-values < .05 were considered significant.

Survival results were last updated in March 2006. Disease-free survival (DFS) was defined as the elapsed time between the date of first diagnosis and the date of first relapse (local, contralateral, and distant event), whatever this relapse might be. OS was the time between the date of initial diagnosis and the date of the last status report, with the patient being alive or dead, whatever the cause of death. Survival curves were established according to the Kaplan–Meier method.

The log-rank test was used for univariate comparisons of survival endpoints. A stepwise Cox regression procedure was carried out to assess the relative influence of prognostic factors on OS and DFS.


   RESULTS
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 Conclusion
 Disclosure of Potential...
 References
 
HR Status in the Population
Among the 420 tumors, 145 (35%) were HR negative and 275 (65%) were HR positive before NCT. When HR status was retested on the surgical specimen (HR status post-NCT), it had changed in 98 patients (23%) among these 420 tumors: 61 patients (42%) initially HR negative became HR positive, and 37 patients (13%) initially HR positive became HR negative.

Among the 61 tumors that had switched to a positive status, 51 (84%) were treated with an anthracycline during NCT, five (8%) were treated with a taxane, and five (8%) were treated with both. Forty patients were treated with adjuvant hormonal therapy and 21 patients did not receive any adjuvant hormonal therapy after surgery. This treatment had no significant impact on the OS and DFS in these groups (p = .55 and p = .37).

Among the 37 tumors that had switched to a negative status, 28 (76%) were treated with an anthracycline during NCT, five (13%) were treated with a taxane, and four (11%) were treated with both. Fourteen patients were treated with adjuvant hormonal therapy and 23 patients did not receive any adjuvant hormonal therapy after surgery. This treatment had no significant impact on the OS and DFS in these groups (p = .68 and p = .93).

DFS and OS
The OS and DFS curves are shown in Figure 1 and Figure 2. OS and DFS were compared between patients with a stable HR-negative status and those who had switched to a positive status after NCT. This HR-positive switch was significantly correlated with better OS (p = .045) and DFS (p = .039) (Figs. 1 and 2).


Figure 1
View larger version (9K):
[in this window]
[in a new window]

  		Figure 1. OS in initially HR-negative patients. Shown are OS curves of patients remaining HR negative (curve 1) and those who had switched to an HR-positive status (curve 2) after NCT.

Abbreviations: HR, hormone receptor; NCT, neoadjuvant chemotherapy; OS, overall survival.

 


Figure 2
View larger version (10K):
[in this window]
[in a new window]

  		Figure 2. DFS in initially HR-negative patients. Shown are DFS curves of patients remaining HR negative (curve 1) and those who had switched to an HR-positive status (curve 2) after NCT.

Abbreviations: DFS, disease-free survival; HR, hormone receptor; NCT, neoadjuvant chemotherapy.

 
Conversely, among the 275 HR-positive tumors, 37 (13%) had become negative after NCT. OS and DFS were compared between patients with a stable HR-negative status and those who had switched to a negative status after NCT. This HR-negative switch was significantly correlated with better OS (p = .036) (Fig. 3). No significant effect was observed for DFS (p = .37) (Fig. 4).


Figure 3
View larger version (9K):
[in this window]
[in a new window]

  		Figure 3. Shown are OS curves of HR-negative patients who remained HR negative (curve 1) and HR-positive patients who became HR negative (curve 2) after NCT.

Abbreviations: HR, hormone receptor; NCT, neoadjuvant chemotherapy; OS, overall survival.

 


Figure 4
View larger version (10K):
[in this window]
[in a new window]

  		Figure 4. Shown are DFS curves of HR-negative patients who remained HR negative (curve 1) and HR-positive patients who became HR negative (curve 2) after NCT.

Abbreviations: DFS, disease-free survival; HR, hormone receptor; NCT, neoadjuvant chemotherapy.

 
Then, OS and DFS were compared between patients with a stable HR-positive status and patients with an HR-positive switch after NCT. No difference was observed for either OS (p = .52) or DFS (p = .81) between these two groups (data not shown).

Multivariate Analysis
The stepwise Cox regression procedure revealed that prognostic factors for OS were nodal involvement (p = 1.2 x 10–7) post-NCT followed by postchemotherapy SBR grade (p = .00015). Postchemotherapy HR status (p = .078) was less correlated with OS in the multivariate analysis than SBR and nodal involvement postchemotherapy. DFS was significantly related to nodal involvement (p = 1.2 x 10–7) postchemotherapy followed by postchemotherapy SBR grade (p = .00015) and postchemotherapy HR status (p = .0078). All other variables tested were not significant.

Hence, this multivariate analysis revealed that postchemotherapy SBR grade and nodal involvement post-NCT are prognostic factors for OS and DFS. Postchemotherapy HR status was a prognostic factor for DFS in the multivariate analysis.

Allred Score
The Allred score was analyzed in 420 tumors for ER status, and in 246 of 420 tumors (174 missing data) for PgR status. The Allred score for ER and PgR was analyzed on tumors whose HR status had become positive after NCT (61 patients). OS and DFS were analyzed for this group. These 61 patients were divided into two groups, one with an Allred score of 0–2 and the second with an Allred score of 3–8. DFS and OS are shown in Figure 5 and Figure 6. An increase in Allred score after NCT, for ER and PgR, was significantly correlated with better DFS (p = .040 and p = .018, respectively) (Figs. 5 and 6). However, this increase in Allred score for ER and PgR status was not significantly correlated with better OS (data not shown; p = 0.14 for ER and p = .058 for PgR).


Figure 5
View larger version (9K):
[in this window]
[in a new window]

  		Figure 5. DFS in patients with an increased ER Allred score after NCT. Shown are DFS curves for patients who had an ER Allred score of 0–2 before NCT. Curve 1, patients whose ER Allred score remained at 0–2 after NCT; curve 2, patients whose ER Allred score increased to 3–8 after NCT.

Abbreviations: DFS, disease-free survival; ER, estrogen receptor; NCT, neoadjuvant chemotherapy.

 


Figure 6
View larger version (10K):
[in this window]
[in a new window]

  		Figure 6. DFS in patients with an increased PgR Allred score after NCT. Shown are DFS curves for patients who had a PgR Allred score of 0–2 before NCT. Curve 1, patients whose PgR Allred score remained at 0–2 after NCT; curve 2, patients whose PgR Allred score increased to 3–8 after NCT.

Abbreviations: DFS, disease-free survival; NCT, neoadjuvant chemotherapy; PgR, progesterone receptor.

 
This analysis showed that the Allred score was very high in 24 patients (Allred score, 7–8) who had switched to a positive HR status after NCT.


   DISCUSSION
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
Conclusion
 Disclosure of Potential...
 References
 
Nowadays, adjuvant hormonal therapy remains the most efficient adjuvant treatment for HR-positive breast cancer, with a gain in DFS of around 15% at 15 years in a meta-analysis database [16]. Patients treated with this therapy are traditionally selected by an assessment of their HR status. It is generally accepted that an HR-positive status predicts response to adjuvant hormonal therapy.

However, HR status variability in human breast cancer has been reported by subsequent assays of ER and PgR status [17].

The first reason is technical, and a recent study has shown a discordance rate in HR status of 9% between core biopsy and surgical specimen [18]. This discordance can be favored by fixation or technical artifacts of IHC [17, 18]. To assess such technical variabilities, we decided to retest all the cases with a validated assay, processed in large series for homogeneity of the stainings. In our study, the discordance rate of HR status was evaluated in 100 patients not treated with NCT as a control group. The discordance rate was very low (3%) between biopsy and surgical specimen for HR status. Although some of the discordance observed in our series might be caused by technical caveats, our controls suggest that these differences are rare and had minor clinical significance.

The second reason is related to described differences between successive samples of the same tumor according to disease dissemination. In the literature, discordance in ER and PgR status has been shown in the same patient, between primary and metastatic tumors [6]. In the retrospective study of Lower et al. [6], the patients whose tumors shifted from negative (primary tumors) to positive (metastatic tumors) status had better OS. This appears different from more constant biologic parameters, such as HER-2 overexpression [2, 3].

The third reason could be changes induced by the treatment itself. In this approach, NCT is a good model in the primary tumor that can be studied before therapy and at subsequent surgery, after NCT. In our study, we reanalyzed HR status and its impact on OS and DFS in 420 operable breast cancer patients, from a greater series of 710 patients treated between 1982 and 2004 with NCT. Selection was only done from available material to reach a paired re-evaluation. The results showed that a change in HR status was frequent after NCT, as it was obtained in 23% of the cases. The change was not a pure biologic modification, as it bore the usual better prognosis observed in HR-positive tumors [19]. In particular, those patients with HR-negative tumors who had switched to a positive status after NCT had better OS and DFS than patients whose tumors remained HR negative after NCT. Conversely, results for the patients who initially had an HR-positive status and became HR negative after NCT are more difficult to understand. For these patients, we observed an advantage in terms of OS but not DFS, when compared with the survival of stable HR-negative patients. When we compared this HR-negative switch population with the stable HR-positive population, we observed no significant difference (data not shown; p = .43). This advantage in term of OS could be explained, in part, by a stronger prognostic value of HR status before than after NCT in this subgroup population. The multivariate analysis confirmed that the switch in HR status could be a prognostic factor for DFS. This has to be considered in relation to other findings of our team using the same database. Residual disease is important for prognosis, and its characteristics need to be considered for an eventual adjuvant treatment [8].

We found it important to assess the magnitude of change: the Allred score helped us to evaluate the impact of the switch in a "semiquantitative" way. We analyzed the group of patients who had switched from an initially HR-negative tumor status. Forty-nine of 61 tumors (80%) shifted to an Allred score of 3–8 after NCT. Among them, 24 tumors became strongly positive (Allred score, 7–8) after NCT treatment and this showed that conversion was often rather striking. Nevertheless, no significant effect was observed on OS.

Two main hypotheses can be generated to explain this high HR status discordance. First of all, this could be the result of a selection of tumor clones during treatment, with a selective disappearance of either HR-positive or HR-negative tumor cells. It is generally known that HR-negative tumors are more sensitive to chemotherapy than HR-positive tumors. Selective changes could also occur in responding patients.

Another explanation would be that receptors could be re-expressed in the tumor cells. All tumor cells are derived from a differentiated breast cell, possessing HRs. The switch in HR status (initially negative and becoming positive after NCT) in some clones could be the result of therapy-induced re-expression of HRs on the nuclei of the tumor cells. For example, chemotherapy could upregulate some proteins implicated in ER expression favoring the expression or re-expression of HRs in the tumor nuclei [20].

However, whatever the reason for this HR status switch, it was significantly correlated with the OS and DFS of patients. Some patients received adjuvant hormonal treatment, whose effect on survival was not significant. We could not exclude interference in the prescription of such treatments, when the multidisciplinary committee met for adjuvant treatment decision. This decision could have been influenced by the clinician reporting on each individual case.


   CONCLUSION
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
Disclosure of Potential...
 References
 
Abrial et al. [8] have previously shown that residual disease after NCT, rather than parameters evaluated on initial biopsy, must be considered for patient prognosis. In this study, survival after NCT was related to the HR status of the residual disease. Furthermore, the high level of discordance in HR status between the initial biopsy and the remaining tumor at surgery underlines the importance of taking into account the HR status of the residual disease after NCT, rather than the HR status on the initial biopsy. It remains to be demonstrated whether or not adjuvant hormonal treatment would be effective in this case; however, this clinical fact is of potential importance.


   DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Disclosure of Potential...
References
 
The authors indicate no potential conflicts of interest.


   REFERENCES
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Disclosure of Potential...
 References
 

  1. Buchholz TA, Hunt KK, Whitman GJ et al. Neoadjuvant chemotherapy for breast carcinoma: Multidisciplinary considerations of benefits and risks. Cancer 2003;98;(6):1150–1160.[CrossRef][Medline]
  2. Simon R, Nocito A, Hubscher T et al. Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst 2001;93:1141–1146.[Abstract/Free Full Text]
  3. Di Leo A, Dowsett M, Horten B et al. Current status of HER2 testing. Oncology 2002;63(suppl 1):25–32.[CrossRef][Medline]
  4. Miyoshi Y, Kim SJ, Akazawa K et al. Down-regulation of intratumoral aromatase messenger RNA levels by docetaxel in human breast cancers. Clin Cancer Res 2004;10:8163–8169.[Abstract/Free Full Text]
  5. Arpino G, Weiss HL, Clark GM et al. Hormone receptor status of a contralateral breast cancer is independent of the receptor status of the first primary in patients not receiving adjuvant tamoxifen. J Clin Oncol 2005;23:4585–4587.[Free Full Text]
  6. Lower EE, Glass EL, Bradley DA et al. Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat 2005;90:65–70.[CrossRef][Medline]
  7. Nicolini A, Giardino R, Carpi A et al. Metastatic breast cancer: An updating. Biomed Pharmacother 2006;60:548–556.[CrossRef][Medline]
  8. Abrial SC, Penault-Llorca F, Delva F et al. High prognostic significance of residual disease after neoadjuvant chemotherapy: A retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat 2005;94:255–263.[CrossRef][Medline]
  9. Belembaogo E, Feillel V, Chollet P et al. J Neoadjuvant chemotherapy in 126 operable breast cancers. Eur J Cancer 1992;28A:896–900.[CrossRef]
  10. Chollet P, Charrier S, Brain E et al. Clinical and pathological response to primary chemotherapy in inoperable breast cancer. Eur J Cancer 1997;33:862–866.[CrossRef][Medline]
  11. Chollet P, Amat S, Penault-Llorca F et al. High pathological response rate induced by primary docetaxel monotherapy in operable breast cancer. Breast Cancer Res Treat 2000;64:251a.
  12. Van Praagh I, Amat S, Delva R et al. Induction chemotherapy in operable breast cancer by NET regimen: Multicentric phase II trial (Meeting abstract). Proc Am Soc Clin Oncol 2001;20:1889a.
  13. Van Praagh I, Curé H, Leduc B et al. Efficacy of a primary regimen combining vinorelbine, epirubicin, and methotrexate (VEM) as neoadjuvant treatment in 89 patients with operable breast cancer. The Oncologist 2002;7:418–423.[Abstract/Free Full Text]
  14. Amat S, Penault-Llorca F, Cure H et al. Scarff-Bloom-Richardson (SBR) grading: A pleiotropic marker of chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant chemotherapy. Int J Oncol 2002;20:791–796.[Medline]
  15. Harvey JM, Clark GM, Osborne CK et al. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17:1474–1481.[Abstract/Free Full Text]
  16. Early Breast Cancer Trialists' Collaborative Group. Cochrane Database Syst Rev. Tamoxifen for early breast cancer, 1, 2001. CD000486.
  17. Davis BW, Zava DT, Locher GW et al. Receptor heterogeneity of human breast cancer as measured by multiple intratumoral assays of estrogen and progesterone receptor. Eur J Cancer Clin Oncol 1984;20:375–382.[CrossRef][Medline]
  18. Mann GB, Fahey VD, Feleppa F et al. Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer. J Clin Oncol 2005;23:5148–5154.[Abstract/Free Full Text]
  19. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. The Oncologist 2004;9:606–616.[Abstract/Free Full Text]
  20. Yang X, Phillips DL, Ferguson AT et al. Synergistic activation of functional estrogen receptor (ER)-{alpha} by DNA methyltransferase and histone deacetylase inhibition in human ER-{alpha}-negative breast cancer cells. Cancer Res 2001;61:7025–7029.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 The OncologistHome page
F. Penault-Llorca, C. Abrial, I. Raoelfils, P. Chollet, A. Cayre, M.-A. Mouret-Reynier, E. Thivat, F. Mishellany, P. Gimbergues, and X. Durando
Changes and Predictive and Prognostic Value of the Mitotic Index, Ki-67, Cyclin D1, and Cyclo-oxygenase-2 in 710 Operable Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
Oncologist, December 1, 2008; 13(12): 1235 - 1245.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. S. Steeg
Heterogeneity of Drug Target Expression Among Metastatic Lesions: Lessons from a Breast Cancer Autopsy Program
Clin. Cancer Res., June 15, 2008; 14(12): 3643 - 3645.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tacca, O.
Right arrow Articles by Chollet, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tacca, O.
Right arrow Articles by Chollet, P.

HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
THE ONCOLOGIST STEM CELLS CME ALPHAMED PRESS JOURNALS