Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9011-2
Annals of Surgical Oncology 13:1434-1442 (2006)
© 2006 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Loibl, S.
Right arrow Articles by Kaufmann, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loibl, S.
Right arrow Articles by Kaufmann, M.

Original Article

Surgical Procedures After Neoadjuvant Chemotherapy in Operable Breast Cancer: Results of the GEPARDUO Trial

Sibylle Loibl, MD1,2, Gunter von Minckwitz, MD1,2, Günther Raab, MD3,11, Jens-Uwe Blohmer, MD4, Serban Dan Costa, MD5, Bernd Gerber, MD6, Holger Eidtmann, MD7, Simone Petrich, MD1, Jörn Hilfrich, MD8, Christian Jackisch, MD9, Andreas du Bois, MD10 and Manfred Kaufmann, MD1

1 Department of Obstetrics and Gynecology, J. W. Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
2 German Breast Group, Neu-Isenburg, Germany
3 Praxis, Maximilianstrasse 50, 80538, München, Germany
4 St. Gertrauden Krankenhaus, Berlin, Germany
5 Department of Obstetrics and Gynecology, Otto-von-Guericke-University, Magdeburg, Germany
6 Department of Obstetrics and Gynecology, Klinikum Süd, Rostock, Germany
7 Department of Obstetrics and Gynecology, Christian-Albrecht-University, Kiel, Germany
8 Henriettenstiftung, Hannover, Germany
9 Klinikum Offenbach, Offenbach, Germany
10 HSK, Dr. Horst Schmidt Klinik, Wiesbaden, Germany
11 Wolfartklinik, Waldstrasse 7, 82166, Gräfelfing, Germany

Correspondence: Address correspondence and reprint requests to: Sibylle Loibl, MD; E-mail: loibl{at}em.uni-frankfurt.de


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery in patients with operable breast cancer. However, uncertainty remains regarding surgical procedures and predictors for successful breast-conserving surgery.

Methods: This study was an analysis of surgical data of a representative data subset of 607 patients enrolled in the GEPARDUO study. This prospective, multicenter, phase III study randomly assigned patients with operable breast cancer (≥ 2 cm) to neoadjuvant 8-week dose-dense doxorubicin plus docetaxel or a 24-week schedule of doxorubicin plus cyclophosphamide followed by docetaxel (AC-DOC).

Results: Breast conservation was attempted in 493 (81.2%) patients, but 43 patients eventually required mastectomy, thus resulting in a breast-conserving surgery rate of 74.1%. Breast-conserving re-excision was performed in 61 patients (12.4%). Factors associated with a significantly higher breast-conserving surgery rate were a prechemotherapy tumor size ≤ 40 mm, nonlobular histological characteristics, treatment with AC-DOC, clinical response, postchemotherapy tumor size ≤ 20 mm, and treatment in a larger center (>10 enrolled patients). Nonlobular histological characteristics and intraoperative frozen-section analysis for margin evaluation were associated with significantly lower reoperation rates (P = .015).

Conclusions: Breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, tumor characteristics and response to neoadjuvant chemotherapy should be taken into account. Improved breast-imaging modalities are necessary to improve detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. Margin assessment by intraoperative frozen-section analysis is helpful to avoid reoperation. To achieve an optimal result, an interdisciplinary surgical approach is important.

Key Words: Neoadjuvant therapy • Breast cancer • Breast conservation • Surgery • Re-excision


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Neoadjuvant or preoperative chemotherapy has been widely accepted as a standard of care in patients with inoperable as well as operable breast cancer.1 The aim of preoperative systemic treatment in patients with locally advanced disease is to achieve local control when this cannot be attained by surgical means alone.2 For patients with operable disease, several large randomized trials comparing preoperative with postoperative adjuvant systemic therapy have shown comparable outcome and safety.3–6 A pathologic complete response (pCR) after preoperative chemotherapy correlates strongly with improved disease-free and overall survival.7–10 Besides allowing assessment of tumor response to a particular chemotherapy regimen, the most appealing advantages of the neoadjuvant approach are that it can induce tumor shrinkage, improve operability, and increase the rate of breast-conserving surgery.4,8,11–13 Even selected patients with T4 tumors have successfully been treated with breast-conserving surgery.14 Therefore, neoadjuvant chemotherapy is now being considered an alternative to adjuvant therapy for patients with operable disease, especially for patients who would otherwise require mastectomy.15 Nevertheless, some concerns remain regarding locoregional control for patients undergoing breast-conserving surgery after neoadjuvant chemotherapy, because resecting the tumor in its new margins bears the risk of leaving microscopic tumor cells behind.16 Several attempts have been made to identify predictors for successful breast conservation after neoadjuvant chemotherapy, including preoperative and postoperative tumor characteristics such as tumor presentation on mammography and residual pathologic tumor size.17,18 However, selection criteria remain controversial, and no standardized protocols exist for the type and extension of breast-conserving surgery after neoadjuvant chemotherapy.

We recently reported the results of the GEPAR-DUO study, a neoadjuvant phase III study, which compared 8-week dose-dense doxorubicin plus docetaxel (ADOC) with a 24-week sequential schedule of doxorubicin plus cyclophosphamide followed by docetaxel (AC-DOC) in 913 patients with operable breast cancer and showed superiority of the AC-DOC regimen with respect to the pathologic response rate.19 The purpose of this study was to further analyze the details of the surgical procedures used in the GEPARDUO trial, focusing on the surgical techniques and the patient and tumor characteristics associated with successful breast-conserving surgery.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between 1999 and 2001, 913 patients with untreated operable breast cancer (T2/3N0–2M0) were enrolled in the GEPARDUO study, a prospective, randomized, phase III study that was conducted in 77 German centers and that compared 2 neoadjuvant chemotherapy regimens.19 For the current analysis, surgical and pathologic reports from 58 centers (75%) could be retrospectively collected and were centrally reviewed (S.L. and S.P.) and linked to the existing GEPARDUO database. The remaining 19 centers did not send in the reports. A selection bias cannot be excluded. Lumpectomy eligibility before neoadjuvant treatment was not assessed. Data extracted from the surgical and pathologic reports included information on surgical techniques, the number and type of re-excisions, preoperative localization of the tumor site, intraoperative frozen-section analysis for margin evaluation, and reconstruction.

Patients in the GEPARDUO trial were randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 each on day 1 every 14 days for four cycles with granulocyte colony-stimulating factor support (ADOC) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles (AC-DOC). Assessment of response was made by palpation and the most appropriate imaging method (ultrasonography, mammography, or magnetic resonance imaging). Surgery was performed within 14 to 28 days after administration of the last chemotherapy cycle. If the tumor was still too large for breast conservation, modified radical mastectomy was recommended. The patients were offered autologous or heterologous reconstructive surgery. If the tumor size allowed breast conservation, the following had to be considered:

  1. Surgical margins should be free of invasive or noninvasive breast cancer. Otherwise, re-excision (breast-conserving re-excision or mastectomy) had to be performed.
  2. Adequate cosmetic results should be anticipated.
  3. If cosmetically acceptable, the entire previously involved area of the breast could be excised. Otherwise (e.g., in case of a clinically complete response and an unfavorable relation of tumor to breast size), a biopsy sample of adequate size should be taken from a representative area. In this case, a wire-guided biopsy was recommended.

All patients undergoing breast-conserving surgery received standard irradiation of the remaining breast after recovery from the operation. Application of the sentinel node biopsy technique was allowed in patients with tumors <2 cm and clinically uninvolved lymph nodes. A pCR was defined as no microscopic viable tumor cells (invasive or noninvasive) in the excised breast specimens and axillary lymph nodes.19

Descriptive data analysis was performed by using the SPSS software package, version 12.0 (SPSS, Inc., Chicago, IL). Statistical comparisons between groups were assessed by the {chi}2 test. All comparisons were two tailed. A P value ≤.05 was considered statistically significant. For each evaluated variable, analysis was restricted to the cases with known values for the factor.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Surgical reports of 607 (65%) of the 913 patients who were enrolled in the GEPARDUO study were available. The distribution of the patient, tumor, and treatment characteristics of the study population in this analysis is comparable to that in the main analysis of the GEPARDUO study, for which details on the studied chemotherapy regimen and analysis of the primary and secondary study end points were already presented and discussed.19

Patient and tumor characteristics at the time of breast cancer diagnosis are summarized in Table 1Go. Among the 607 patients studied in the current analysis, 306 had randomly been assigned to ADOC and 301 to AC-DOC. The median clinical tumor size was 40 mm (range, 15–160 mm) before and 10 mm (range, 0–85 mm) after neoadjuvant chemotherapy. The clinical response rates (complete and partial response) assessed by palpation and imaging were 77.4% and 69.5%, respectively. The pCR rate in this subset of patients was 8.5% for ADOC and 15% for AC-DOC (P < .001), as compared with 7.0% and 14.3%, respectively, in the main analysis.


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

  		TABLE 1. Patient and tumor characteristics at diagnosis (N = 607)
 
An attempt to achieve breast conservation was made in 493 (81.2%) patients, but 43 of these patients eventually required mastectomy, thus resulting in an overall breast-conserving surgery rate of 74.1%. Re-excision (breast-conserving re-excision or subsequent mastectomy) was performed in 104 patients (21.1%) because final pathologic analysis showed involved or close margins. Breast-conserving re-excision was possible in 61 (60%) patients, whereas 39, 3, and 1 patients ultimately received mastectomy as a second, third, or fourth operation, respectively (Table 2Go). One patient required re-excision after primary mastectomy to achieve free margins. The incidence of residual cancer in the re-excised tissue was 42.2%, and most (63.3%) of the tumor residuals were invasive. Eighteen patients (7 after breast conservation and 11 after mastectomy) with involved margins did not receive re-excision, for unknown reasons.


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

  		TABLE 2. Type of surgery
 
Breast-conserving surgery was combined with reconstructive procedures in 35.3% of the cases; a local glandular flap was the most frequently used technique (27.6%). Breast reconstruction after mastectomy included the use of heterologous material (implants) and autologous tissue (latissimus dorsi flap and transverse rectus abdominis myocutaneous flap) and was applied in 30.6% of the patients (Table 2Go).

Placement of a titan clip to mark the tumor before commencement of chemotherapy was used in 7% of the patients. Preoperative localization of the tumor either by ultrasound- or radiographic-guided wire placement or ultrasound-guided dye application was used in 194 patients (32.2%) and was more frequently applied in case of a clinical complete response (43.9%). Two patients received preoperative localization by magnetic resonance imaging–guided wire placement. Conventional axillary node dissection was performed in most patients (n = 604; 99.3%), whereas only 3 patients were treated by sentinel node biopsy. One patient did not receive axillary dissection, for unknown reasons. The mean number of removed axillary lymph nodes was 15 (range, 1–54). In 49 patients (8.1%), fewer than 10 lymph nodes were removed.

The breast-conserving surgery rate was significantly higher among patients who had received AC-DOC compared with patients treated with ADOC (78.1% vs. 70.3%; P < .028). Patients with a clinical complete response after neoadjuvant chemotherapy were more likely to receive breast-conserving surgery than patients with a partial response or with stable or progressive disease. The type of surgery correlated strongly with clinical tumor size after chemotherapy (P < .0001). Patients treated by tumorectomy had a mean tumor diameter of 10.9 mm after chemotherapy, as compared with 22.3 mm in the mastectomy group (Fig. 1Go). Ductal invasive breast cancer histology was associated with a higher breast-conservation rate than lobular invasive histology (78.6% vs. 61.0%; P < .0001).


Figure 1
View larger version (14K):
[in this window]
[in a new window]

  		FIG. 1. Bar chart with mean tumor sizes before chemotherapy (36.9, 38.8, and 40.2 mm) and after chemotherapy (before surgery; 10.9, 11.4, and 22.3 mm) according to the different surgical procedures. The correlation between the tumor size after chemotherapy and the surgical procedure was significant (P < .0001).

 
When centers were divided into 2 groups according to the number of patients enrolled, the 469 patients treated in one of the 18 larger centers (≥10 enrolled patients) were more likely to receive breast-conserving surgery (77.8%) than 138 patients treated in one of the 40 smaller centers (<10 enrolled patients) (62.3%; P < .0001). The median clinical tumor size after chemotherapy did not differ (13 vs. 14 mm), and treatment regimens were balanced (n = 236 for ADOC vs. n = 233 for AC-DOC) in centers recruiting more or less than 10 patients. All preoperative characteristics analyzed for a possible association with breast-conserving surgery rate are summarized in Table 3Go.


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

  		TABLE 3. Breast-conserving surgery as a final result (N = 450) according to preoperative
 
Univariate and multivariate analysis of postoperative pathologic data showed significantly higher breast-conserving surgery rates for patients with pCR, a negative pathologic lymph node status, absence of lymphovascular space invasion, and uni-focal disease (Table 4Go).


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

  		TABLE 4. Breast-conserving surgery as a final result (N = 450) according to postoperative variables
 
The re-excision rate after attempted breast conservation was significantly higher in patients with lobular invasive tumors than in patients with ductal invasive carcinomas or other histological diagnoses (32.4%, 14.6%, and 8.8%, respectively; P < .0001). The pCR rate for ductal invasive cancers was 12.8% and was 4.8% for lobular invasive cancers (P = .025). Re-excision after lumpectomy was more frequent than after segmentectomy or quadrantectomy (24.1% vs. 19.3%), but this did not reach statistical significance (P = .21). If an intraoperative frozen-section analysis for margin evaluation was performed, the re-excision rate was significantly lower (13.3% vs. 27.0%; P < .0001). All factors studied for possible association with the re-excision rate are listed in Table 5Go.


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

  		TABLE 5. Re-excision rate after attempted breast conservation (N = 493) according to different factors
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Breast-conserving surgery after neoadjuvant chemotherapy in patients with operable breast cancer is challenging, especially when the tumor responded well to systemic treatment. The current analysis of 607 (65%) of the 913 patients enrolled in the GEPARDUO study gives detailed information on the surgical procedures applied after neoadjuvant chemotherapy.

More than 70% of the patients in our study were treated by breast conservation. Free margins could mostly be achieved with the first surgical procedure, but 21.1% of the patients required re-excision either by breast-conserving surgery (12.4%) or mastectomy (8.7%). Preoperative planning and intraoperative macroscopic evaluation of the tumor-free margins seem more difficult after tumor downstaging by pre-operative systemic therapy, and this leads to additional surgical procedures. Re-excision rates after breast-conserving surgery after neoadjuvant chemotherapy have rarely been reported.4 Sadetzki et al.18 studied 100 patients with stage II and III breast cancer who were designated for lumpectomy after neoadjuvant chemotherapy. Nineteen percent of the patients proceeded to mastectomy, and 10% required re-excision lumpectomy. The higher rate of secondary mastectomies may be explained by the inclusion of patients with larger tumors, with a mean tumor size of 50 mm before chemotherapy compared with 40 mm in our study, as well as the use of a non–taxane-containing regimen. The frequency of residual cancer in re-excised tissue for close or positive margins was 42% and is comparable to the frequency observed after primary breast-conserving surgery (without prior systemic treatment).20,21

Conversion of patients who were initially candidates for mastectomy into candidates for breast conservation can be considered the most appealing benefit of neoadjuvant chemotherapy in patients with operable breast cancer.4,22 Optimizing neoadjuvant treatment has been shown to improve response rates and often translates into increased breast-conservation rates.23,24 Unfortunately, we were unable to retrospectively determine the percentage of patients eligible for breast-conserving surgery up front. However, the fact that the breast-conservation rate was improved with the more effective AC-DOC treatment in the GEPARDUO study indicates that surgeons took advantage of the observed tumor shrinkage by resecting the breast tumor according to its new margins. The frequent use of a lumpectomy as a surgical technique to achieve breast conservation in our analysis supports this hypothesis.

When performing a lumpectomy, the surgeon is guided by the (residual) breast mass and therefore most likely operates according to its new margins. Some authors have reported higher re-excision rates after lumpectomy as opposed to quadrantectomy in patients treated by primary surgery.25,26 Although there was a trend toward more frequent re-excisions in patients receiving lumpectomy in this analysis, this did not reach statistical significance. Intraoperative frozen-section analysis of margins was associated with a significantly lower re-excision rate in our study (13.3% vs. 27.0%) and might therefore be a useful instrument to minimize reoperation after attempted breast conservation. Data on the use of intraoperative margin assessment after neoadjuvant chemotherapy have not been reported to date, but a comparable reduction in number of re-excisions has been demonstrated for intraoperative margin assessment in patients undergoing primary breast-conserving surgery.27,28

Most of the factors we found to be associated with a higher breast-conservation rate are related to the initial tumor stage and the response to chemotherapy. Naturally, neoadjuvant chemotherapy is less likely to shrink a large tumor enough to enable breast conservation than it is a small tumor. Larger tumors have also been demonstrated to respond less well to neoadjuvant chemotherapy than smaller tumors.22 However, patients with tumors showing a clinical response to neoadjuvant therapy after the first two cycles have a higher chance to be treated by breast-conserving surgery (86.3%) than patients who did not respond after the first two cycles (66%).29 Special attention needs to be paid to patients with lobular invasive breast cancer histology. Only 56% of the patients with lobular invasive breast cancer were able to undergo breast conservation in our study, and the re-excision rate was significantly higher in these patients. Lobular invasive breast cancer has lower clinical and pathologic response rates after neoadjuvant chemotherapy, and this can be an explanation for the lower breast-conservation rate.30–32 Moreover, the extent of disease is known to be difficult to judge in tumors of lobular histology.

It is interesting to note that the likelihood of a patient’s undergoing breast conservation also depended on treatment center size. Patients treated in large centers, which enrolled ≥10 patients in the GEPARDUO study, were more likely to receive breast-conserving therapy than patients treated in smaller centers, which enrolled <10 patients. The number of enrolled study subjects can be expected to correlate with hospital volume and surgeon experience in our study. This observation has already been reported for nonstudy patients in an epidemiological study in Germany.33 Similar observations have been made by Hiotis et al.,34 who demonstrated that not only the extent of locoregional disease but also hospital volume, surgeon volume, and surgeon specialization, affect the likelihood of a patient’s receiving breast-conserving surgery. Other factors such as socioeconomic status and patient choice have been demonstrated to influence breast-conservation rates as well, but this study focused on retrospective collection of surgical and pathologic reports only.34,35

One difficulty of breast-conserving surgery after neoadjuvant chemotherapy lies in the limited ability to predict which patients will have a pCR. The main analysis of the GEPARDUO study revealed that neither palpation nor any of the imaging techniques used to assess tumor response were associated with a meaningful positive predictive value for pCR of the breast tumor.19 Nevertheless, imaging techniques can be helpful in determining the location and extent of residual disease and facilitate surgery.18,36 In this study, one third of the patients received ultrasound-or mammography-guided preoperative localization of the tumor site. Although breast conservation could be achieved in most of these patients, the number of re-excisions was still 22.3%, thus suggesting that more accurate methods of detecting residual tumor after neoadjuvant chemotherapy are necessary. Magnetic resonance imaging, which was applied to evaluate the tumor response in 7.6% of the study population only, might be superior to other imaging techniques in identifying residual lesions, but this has not yet been fully established.37,38 To overcome the difficulty of later localization of the tumor site in patients with a clinical complete response to neoadjuvant chemotherapy, different techniques of marking the tumor bed either before initiation of chemotherapy or after the first cycle, according to response, have been advocated: (1) invasive procedures, such as placement of metallic markers or platinum embolization coils or marking the position and size of the tumor on the breast skin with a tattoo, and (2) noninvasive techniques, such as preparing a transparent grid or sketch and photographing the breast and tumor location.15,35,39,40 Only 7% of the patients in our analysis received placement of a titan clip before chemotherapy began, but information on the number and kind of noninvasive tumor markings by drawing or photography was not available and could therefore not be analyzed. In all protocols of consecutive neoadjuvant chemotherapy studies conducted by the German Breast Group, marking of the primary tumor site is recommended, according to Kaufmann et al.15

Recently, Chen et al.41 presented the M.D. Anderson prognostic index as an instrument for selecting patients for breast conservation after neo-adjuvant chemotherapy on the basis of their risk of developing local failure. Factors predictive of increased local failure rates in their study (e.g., multi-focal disease and lymphovascular space invasion) were similar to the postoperative variables associated with lower breast-conservation rates in our study. Unfortunately, most factors associated with increased local failure in Chen and associates’ study can be determined only after surgery and are therefore not available for initial surgical procedure planning.

Our study has several limitations. First, we could not measure the cosmetic benefit many patients may have experienced, because tumor shrinkage after neoadjuvant chemotherapy allowed resection of a smaller volume of tissue. Second, this analysis was focused on the practical aspects of surgery after neoadjuvant chemotherapy, and, therefore, data on local failure were not presented. However, analysis of disease-free (intrabreast, local, regional, and distant) and overall survival is in preparation.

In conclusion, the results of this study demonstrate that breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, it is important to take into account the initial tumor stage and clinical response to neoadjuvant chemotherapy. Improved breast-imaging modalities are necessary to improve the accuracy of detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. To facilitate surgery, we recommend marking the tumor site before commencement of chemotherapy and intraoperative frozen-section analysis for margin assessment to avoid reoperation. Surgery after neo-adjuvant chemotherapy for breast cancer is challenging and should therefore be performed by an experienced breast surgeon.


   ACKNOWLEDGMENTS
 
The authors thank Michaela Kandel, MD, who provided medical writing services on behalf of the German Breast Group.

Received for publication November 22, 2005. Accepted for publication February 13, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Kaufmann M, Hortobagyi GN, Goldhirsch A. Recommendations from an international expert panel on the use of neo-adjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006; 24:1940–9.[Abstract/Free Full Text]
  2. Hortobagyi GN, Singletary E, Strom EA. (2000) Treatment of locally advanced and inflammatory breast cancer. In: Harris J, ed. Diseases of the Breast 2nd ed. Lippincott Williams & Wilkins, Philadelphia, pp 645–60.
  3. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998; 16:2483–93.
  4. van der Hage JA, van de Velde CJ, Julien JP, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 2001; 19:4224–37.[Abstract/Free Full Text]
  5. Scholl SM, Fourquet A, Asselain B, et al. Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial—S6. Eur J Cancer 1994; 30A:645–52.[CrossRef]
  6. Broet P, Scholl SM, De la Rochefordiere A, et al. Short and long term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomised trial. Breast Cancer Res Treat 1999; 58:151–6.[CrossRef][Medline]
  7. Scholl SM, Pierga J, Asselain B, et al. Breast tumor response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 1995; 31:1969–75.[CrossRef]
  8. Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17:460–9.[Abstract/Free Full Text]
  9. Chollet P, Amat S, Cure H, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer 2002; 86:1041–106.[CrossRef][Medline]
  10. Thomas E, Holmes FA, Smith TL, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol 2004; 22:2294–302.[Abstract/Free Full Text]
  11. Bonnadonna G, Veronesi U, Brambilla C, et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 1990; 82:1539–45.[Abstract/Free Full Text]
  12. Makris A, Powles TJ, Ashley SE, et al. A reduction of requirements for mastectomy in a randomised trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 1998; 9:1179–84.[Abstract/Free Full Text]
  13. Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997; 15:2483–93.[Abstract/Free Full Text]
  14. Shen J, Valero V, Buchholz TA, et al. Effective local control and long-term survival in patients with T4 locally advanced breast cancer treated with breast conservation therapy. Ann Surg Oncol 2004; 11:854–60.[Abstract/Free Full Text]
  15. Kaufmann M, von Minckwitz G, Smith R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21:2600–8.[Abstract/Free Full Text]
  16. Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a metaanalysis. J Natl Cancer Inst 2005; 97:188–94.[Abstract/Free Full Text]
  17. Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy. Cancer 2005; 103:689–95.[CrossRef][Medline]
  18. Sadetzki S, Oberman B, Zipple D, et al. Breast conservation after neoadjuvant chemotherapy. Ann Surg Oncol 2005; 12:1–8.[Free Full Text]
  19. von Minckwitz G, Raab G, Caputo A, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as pre-operative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 2005; 23:2676–85.[Abstract/Free Full Text]
  20. Papa M, Zippel D, Koller M, et al. Positive margins of breast biopsy: is reexcision always necessary?. Surg Oncol 1999; 70:167–71.[CrossRef]
  21. Cellini C, Hollenbeck ST, Christis P, et al. Factors associated with residual breast cancer after re-excision for close or positive margins. Ann Surg Oncol 2004; 11:915–20.[Abstract/Free Full Text]
  22. Fisher B, Brown E, Mamounas E, et al. The effect of preoperative chemotherapy on loco-regional disease in women with operable breast cancer: findings from NSABP B-18. J Clin Oncol 1997; 15:2483–93.[Abstract/Free Full Text]
  23. Dieras V, Fumoleau P, Romieu G, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol 2004; 22:4958–65.[Abstract/Free Full Text]
  24. Untch M, Konency G, Ditsch N, et al. Dose-dense sequential epirubicin-paclitaxel as preoperative treatment of breast cancer: results of a randomised AGO study (abstract 133). Proc Am Soc Clin Oncol 2002; 21:34a.
  25. Noh WC, Paik NS, Kim MS. Ipsilateral breast tumor recurrence after breast-conserving therapy: a comparison of quadrantectomy versus lumpectomy at a single institution. World J Surg 2005; 29:1001–6.[CrossRef][Medline]
  26. Veronesi U, Volterrani F, Luini A, et al. Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 1990; 26:671–3.[Medline]
  27. Fleming FJ, Hill AD, McDermott EW, O’Doherty A, O’Higgins NJ, Quinn CM. Intraoperative margin assessment and re-excision rate in breast conserving surgery. Eur J Surg Oncol 2004; 30:233–7.[CrossRef][Medline]
  28. Weber S, Storm FK, Stitt J, Mahvi DM. The role of frozen section analysis of margins during breast conservation surgery. Cancer J Sci Am 1997; 3:273–7.[Medline]
  29. von Minckwitz G, Blohmer JU, Raab G, et al. In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol 2005; 16:56–63.[Abstract/Free Full Text]
  30. Cocquyt VF, Blondeel PN, Depypere HT, et al. Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol 2003; 29:361–7.[CrossRef][Medline]
  31. Mathieu MC, Rouzier R, Llombart-Cussac A, et al. The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer 2004; 40:342–51.[CrossRef][Medline]
  32. Newman LA, Buzdar AU, Singletary SE, et al. A prospective trial of preoperative chemotherapy in resectable breast cancer: predictors of breast-conservation therapy feasibility. Ann Surg Oncol 2002; 9:228–34.[Abstract/Free Full Text]
  33. du Bois A, Misselwitz B, Wagner U, et al. Disease Management Programm (DMP) Brustkrebs und Versorgungsstruktur bei der operativen Therapie des Mammakarzinoms in Hessen 2002. Geburtshilfe Frauenheilkd 2004; 64:261–70.[CrossRef]
  34. Hiotis K, Ye W, Sposto R, Skinner KA. Predictors of breast conservation therapy. Size is not all that matters. Cancer 2005; 103:892–9.[CrossRef][Medline]
  35. Morrow M, Bucci C, Rademaker A. Medical contraindications are not a major factor in the underutilization of breast conserving therapy. J Am Coll Surg 1998; 186:269–74.[CrossRef][Medline]
  36. Kuerer HM, Singletary SE, Buzdar AU, et al. Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma. Am J Surg 2001; 182:601–8.[CrossRef][Medline]
  37. Yeh E, Slanetz P, Kopans DB, et al. Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol 2005; 184:868–77.[Abstract/Free Full Text]
  38. Rosen EL, Blackwell KL, Baker JA, et al. Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol 2003; 181:1275–82.[Abstract/Free Full Text]
  39. Veronesi U, Bonnadonna G, Zurrida S, et al. Conservation surgery after primary chemotherapy in large carcinomas of the breast. Ann Surg 1995; 222:612–8.[Medline]
  40. Margolese RG. Surgical considerations in preoperative chemotherapy of breast cancer. Recent Results Cancer Res 1998; 152:193–201.[Medline]
  41. Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy. A prognostic index for clinical decision-making. Cancer 2005; 103:689–95.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 JNCI J Natl Cancer InstHome page
G. von Minckwitz, S. Kummel, P. Vogel, C. Hanusch, H. Eidtmann, J. Hilfrich, B. Gerber, J. Huober, S. D. Costa, C. Jackisch, et al.
Neoadjuvant Vinorelbine-Capecitabine Versus Docetaxel-Doxorubicin-Cyclophosphamide in Early Nonresponsive Breast Cancer: Phase III Randomized GeparTrio Trial
J Natl Cancer Inst, April 16, 2008; 100(8): 542 - 551.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
G. von Minckwitz, S. Kummel, P. Vogel, C. Hanusch, H. Eidtmann, J. Hilfrich, B. Gerber, J. Huober, S. D. Costa, C. Jackisch, et al.
Intensified Neoadjuvant Chemotherapy in Early-Responding Breast Cancer: Phase III Randomized GeparTrio Study
J Natl Cancer Inst, April 16, 2008; 100(8): 552 - 562.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. Kaufmann, G. von Minckwitz, H. D. Bear, A. Buzdar, P. McGale, H. Bonnefoi, M. Colleoni, C. Denkert, W. Eiermann, R. Jackesz, et al.
Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006
Ann. Onc., December 1, 2007; 18(12): 1927 - 1934.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Loibl, S.
Right arrow Articles by Kaufmann, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loibl, S.
Right arrow Articles by Kaufmann, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS