Annals of Oncology Advance Access originally published online on January 15, 2009
Annals of Oncology 2009 20(6):1008-1012; doi:10.1093/annonc/mdn732
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
breast cancer |
Unavoidable mastectomy for ipsilateral breast tumour recurrence after conservative surgery: patient outcome
1 Division of Epidemiology and Biostatistics
2 Division of Breast Surgery
3 Scientific Director, European Institute of Oncology, Milan, Italy
* Correspondence to: Dr E. Botteri, Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Tel: +39-2-57489820; Fax: +39-2-57489813; E-mail: edoardo.botteri{at}ieo.it.
 |
abstract |
|---|
 Top abstract introductionpatients and methodsresultsconclusionsreferences |
|---|
Background: In the case of ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS), a second conservative surgical approach maybe considered in some motivated patients whereas in others mastectomy is unavoidable.
Patients and methods: From 1997 to 2004, 282 patients presented at the European Institute of Oncology with an operable invasive IBTR after BCS. One hundred and sixty-one (57%) underwent a second conservative surgery, whereas 121 patients (43%) were given a mastectomy and represent the study population. We investigated the prognosis and determined predictive factors of outcome.
Results: Median time from primary breast cancer to IBTR was 41 months (range 5–213). Recurrences were T2–T4 and/or multifocal in 83 cases (68.6%). With a median follow-up of 5 years after mastectomy, 5-year overall survival (OS) and disease-free survival (DFS) were 73.3% [95% confidence interval (CI) 65.0% to 81.6%] and 50.4% (95% CI 40.9% to 59.8%), respectively. At the multivariate analysis, early onset of IBTR, presence of vascular invasion and Ki67 
20 of the recurrent tumour were found to significantly affect both DFS and OS.
Conclusions: In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors.
Key words: breast tumour, breast-conserving surgery, ipsilateral breast recurrence, mastectomy
|
introduction |
|---|
|
Topabstractintroductionpatients and methodsresultsconclusionsreferences |
|---|
Breast conservation is considered the treatment of choice for early breast cancer worldwide, with a similar long-term outcome to mastectomy [1, 2], although a minority of patients treated conservatively will develop ipsilateral breast tumour reappearance (IBTR) [1]. Even if there is growing acceptance of the concept that some patients with IBTR might receive a second breast-conserving surgery (BCS) [3–7], particularly with small and late recurrence, the vast majority of patients with IBTR have so far undergone mastectomy.
At the European Institute of Oncology in Milan, mastectomy is carried out in selected cases of IBTR, when adequate local control cannot be secured, and also in accordance with the patients’ preference. The aim of the present study was to investigate the prognosis and the predictive factors of outcome in a single-institution series.
|
patients and methods |
|---|
|
Topabstractintroductionpatients and methodsresultsconclusionsreferences |
|---|
From April 1997 to December 2004, 12 357 patients were operated for breast cancer at the European Institute of Oncology in Milan. Two hundred and eighty-two consecutive patients with an operable invasive IBTR as a first event and no evidence of synchronous metastatic disease were identified. For the treatment of primary cancer, all patients underwent BCS followed by local radiotherapy extended to lymph node area whenever appropriate. Ninety-nine were operated at our institute for the primary cancer, whereas 183 were initially operated at a different hospital and then referred to our institute for IBTR.
After confirmation of IBTR, all patients underwent physical examination, complete staging [bone scan, chest X-ray, liver ultrasound (US) or computed tomography (CT) scan] and mammography and breast US to rule out multicentricity. Magnetic resonance imaging of the breast was carried out in only a few selected patients. One hundred and sixty-one of 282 patients (57%) underwent a further conservative approach and represent the reference population of a previous study [3]. The other 121 patients received mastectomy (43%) and represent the population of the present study.
Following the second surgery for IBTR, all cases were discussed during the weekly multidisciplinary meeting attended by surgeons, medical oncologists, radiation oncologists and pathologists and received adjuvant systemic treatment according to biological features, staging and treatment previously received. None of the patients received further radiation therapy after surgery. Patients were usually followed up with physical examination every 6 months and mammography with or without breast US every year. In cases with symptoms or when clinically indicated, bone scan, chest X-ray, liver US or CT scan was carried out.
statistical methods
Primary end points were disease-free survival (DFS) and overall survival (OS). DFS was calculated from the date of first IBTR to any relapse, contralateral breast cancer recurrence or death, whichever occurred first, or to the date of last visit in case of no events. OS was defined as the time interval from first IBTR to death from any cause or to the date of last contact. The DFS and OS were plotted using the Kaplan–Meier method. The log-rank test was used to assess survival differences between groups in the univariate analysis. Multivariate Cox proportional hazards regression models were used to identify the prognostic independent clinicopathological features associated with survival.
All analyses were carried out with the SAS software (SAS Institute, Cary, NC). All tests were two sided.
|
results |
|---|
|
Topabstractintroductionpatients and methodsresultsconclusionsreferences |
|---|
Median time to relapse was 41 months (range 5–213). Median age of patients at the occurrence of IBTR was 49 years (range 27–79). Median follow-up was 60 months (range 4–127). One patient died from breast cancer 4 months after surgery for IBTR, representing the shortest period of observation. Table 1 shows patients’ characteristics at presentation of primary breast cancer and at the occurrence of IBTR. Recurrences were T2–T4 and/or multifocal in 83 cases (68.6%). With regards to adjuvant systemic treatment, 28 patients were prescribed both chemo and hormone therapy, 47 only chemo, 45 only hormone and one patient no treatment.
|
With regards to further local relapses, four patients (3.3%) had a recurrence on the chest wall and 14 patients (11.6%) had a skin relapse. Considering all other types of events, 11 patients had a regional event (9.1%), 23 patients distant metastases (19.0%), four patients both local and distant metastases (0.6%) and one patient had a contralateral breast tumour. Death was the first event in eight patients (6.6%).
Overall, 41 patients died during the follow-up, with an OS at 5 years of 73.3% [95% confidence interval (CI) 65.0% to 81.6%; Figure 1A]. We observed an increasing OS with increasing time to IBTR: 5-year OS was 50.9%, 74.0% and 88.4% for time to IBTR 
24, 25–48 and >48 months, respectively (log-rank P value < 0.001, Figure 1B).
|
|
Five-year DFS was 50.4% (95% CI 40.9% to 59.8%; Figure 2A). Again, we observed an increasing DFS with increasing time to IBTR: 5-year DFS was 32.9%, 55.6% and 58.1% for time to IBTR
24, 25–48 and >48 months, respectively (log-rank P value 0.013, Figure 2B).
At the univariate analysis (Table 2), time to IBTR, hormone receptor status, Ki-67 and vascular invasion were found to be associated with DFS and OS and were further analysed in a multivariate model. At the multivariate analysis (Table 3), time to IBTR 24 months, Ki-67 20% and presence of vascular invasion were found to be independently associated with both DFS and OS. In addition, when analysed as a continuous variable, time to IBTR was significantly associated with both OS and DFS in the multivariate model (P value 0.013 and 0.034, respectively).
|
|
|
conclusions |
|---|
|
Topabstractintroductionpatients and methodsresultsconclusionsreferences |
|---|
IBTR represents an alarming event since it is associated with increased risk of distant disease and death [8, 9]. A recent report by the National Surgical Adjuvant Breast and Bowel Project (NSABP), based on 259 patients with invasive IBTR after BCS, reported an OS at 5 years of 59.9%, and a hazard ratio for mortality associated with IBTR of 2.58 [10].
So far, IBTR after breast conservation has been dogmatically treated by mastectomy, even in patients with small and late recurrences. At the European Institute of Oncology, we have a strong stance in favour of breast conservation which we try to carry out whenever possible even in patients with IBTR after BCS. We previously published our experience with repeating breast conservation in patients with IBTR after BCS suggesting that a second conservative procedure might be considered in motivated women with small and late reappearing tumour [3]. In fact, the 5-year cumulative incidence of a further local event after a second conservative procedure was 12.8% in the subset of patients who had a tumour <2 cm reappearing >48 months after the primary treatment. Yet, there are some situations where mastectomy is unavoidable because of the tumour/breast ratio, the presence of multifocality/multicentricity, the poor expected cosmetic result or the patients’ preference and here we report the outcome of those patients who were not deemed suitable for a further conservative surgery. The present series represents indeed a selected population of patients with a high proportion of either large of multifocal tumours. In fact, recurrences were >2 cm or involving the skin and/or multifocal in 83 cases (68.6%). Moreover, poor prognostic features were frequently found (estrogen receptors absent in 45%, Her2/neu overexpressed in 32%, Ki-67 20% in 71%, vascular invasion present in 40%).
In this series of 121 women who underwent mastectomy for invasive IBTR after BCS, 73.3% of patients were alive at 5 years after mastectomy and 50.4% were disease free. Mastectomy did not eliminate the risk of subsequent secondary local recurrences: four women out of 121 (3.3%) had a chest wall recurrence and 14 had a skin relapse (11.6%). Two previous studies reported similar rates of chest wall recurrences [11, 12]. All these data confirm that local recurrence is not an innocent event [13] and that treatment of the primary surgery must be adequate in order to minimise the risk of reappearance.
The median time to IBTR was 41 months suggesting that a large proportion of these patients had a true recurrence. Time to IBTR, which can be considered as a surrogate marker of aggressiveness, was an important prognostic factor for both OS and DFS, thus confirming previous results [8–11, 14–17]. An important proportion of late IBTRs may in fact represent metachronous second primaries in the breast which have more favourable outcomes than persistent, radio-resistant or drug-insensitive recurrences of the primary lesion [8, 18].
In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors. The use of systemic treatment for IBTR after BCS is a matter of debate. Recently, a large international multicenter trial by the International Breast Cancer Study Group and the NSABP was initiated (http://www.ibcsg.org; http://www.nsabp.pitt.edu) to address this issue (IBCSG 27-02/BIG 1-02).
Received for publication September 5, 2008. Accepted for publication November 4, 2008.
|
references |
|---|
|
Topabstractintroductionpatients and methodsresultsconclusionsreferences |
|---|
1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med (2002) 347(16):1227–1232.
2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med (2002) 347(16):1233–1241.
3. Gentilini O, Botteri E, Rotmensz N, et al. When can a second conservative approach be considered for ipsilateral breast tumour recurrence? Ann Oncol (2007) 18(3):468–472.
4. Salvadori B, Marubini E, Miceli R, et al. Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery. Br J Surg (1999) 86(1):84–87.[CrossRef][Web of Science][Medline]
5. Kurtz JM, Jacquemier J, Amalric R, et al. Is breast conservation after local recurrence feasible? Eur J Cancer (1991) 27(3):240–244.[Web of Science][Medline]
6. Deutsch M. Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation. Int J Radiat Oncol Biol Phys (2002) 53(3):687–691.[CrossRef][Web of Science][Medline]
7. Kuerer HM, Arthur DW, Haffty BG. Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence: the potential role of partial breast irradiation. Cancer (2004) 100(11):2269–2280.[CrossRef][Web of Science][Medline]
8. Veronesi U, Marubini E, Del Vecchio M, et al. Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events. J Natl Cancer Inst (1995) 87(1):19–27.
9. Fisher B, Anderson S, Fisher ER, et al. Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet (1991) 338(8763):327–331.[CrossRef][Web of Science][Medline]
10. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol (2006) 24(13):2028–2037.
11. Doyle T, Schultz DJ, Peters C, et al. Long-term results of local recurrence after breast conservation treatment for invasive breast cancer. Int J Radiat Oncol Biol Phys (2001) 51(1):74–80.[Web of Science][Medline]
12. Abner AL, Recht A, Eberlein T, et al. Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer. J Clin Oncol (1993) 11(1):44–48.[Abstract]
13. Punglia RS, Morrow M, Winer EP, Harris JR. Local therapy and survival in breast cancer. N Engl J Med (2007) 356(23):2399–2405.
14. Whelan T, Clark R, Roberts R, et al. Ipsilateral breast tumor recurrence postlumpectomy is predictive of subsequent mortality: results from a randomized trial. Investigators of the Ontario Clinical Oncology Group. Int J Radiat Oncol Biol Phys (1994) 30(1):11–16.[Web of Science][Medline]
15. Haffty BG, Reiss M, Beinfield M, et al. Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse. J Clin Oncol (1996) 14(1):52–57.[Abstract]
16. Touboul E, Buffat L, Belkacemi Y, et al. Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys (1999) 43(1):25–38.[CrossRef][Web of Science][Medline]
17. Fourquet A, Campana F, Zafrani B, et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys (1989) 17(4):719–725.[Web of Science][Medline]
18. Huang E, Buchholz TA, Meric F, et al. Classifying local disease recurrences after breast conservation therapy based on location and histology: new primary tumors have more favorable outcomes than true local disease recurrences. Cancer (2002) 95(10):2059–2067.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||