Abstract
Background
Identification of women treated for breast cancer who have a low risk of locoregional recurrence or contralateral breast cancer, and who can be discharged safely from follow-up, would lower costs without compromising prognosis. This study investigated the risk of locoregional recurrence and contralateral breast cancer in women treated for grade 1 breast cancer.
Methods
Some 1143 women who had surgery for breast cancer were followed, and the rate of locoregional recurrence or contralateral breast cancer was determined. The risk was compared to the tumour grade.
Results
At a mean follow-up of 9·1 years, 10-year estimates of the cumulative risk of locoregional recurrence or contralateral breast cancer for grade 1, 2 and 3 breast cancer were 0·03 (95 per cent confidence interval (c.i.) 0·01 to 0·08), 0·12 (0·09 to 0·15) and 0·16 (0·13 to 0·20) respectively. Grade 1 tumours had a risk of locoregional recurrence or contralateral breast cancer of 285 (95 per cent c.i. 93 to 670) per 100 000 person-years.
Conclusion
Women treated for grade 1 breast cancer could be discharged from follow-up after completion of the primary treatment, without compromising their quality of care.
Potentially curable recurrence was rare
Introduction
Because of the high incidence of breast cancer and the recent advances in its treatment, the number of women surviving is constantly increasing, with a major impact on costs of follow-up. Routine clinical and/or mammographic follow-up is important for the early detection of locoregional recurrence (LRR). The timely diagnosis of LRR makes radical treatment possible and could improve survival for a subgroup of patients1–3. The identification of women with a low risk of recurrent breast cancer who can safely be discharged from follow-up after completion of their primary treatment (surgery plus radiotherapy and/or chemotherapy) would reduce anxiety and lower the cost of care without compromising quality of care or prognosis.
Several scoring systems for the prediction of local or distant recurrence after breast cancer treatment have been suggested, but few have been implemented in clinical practice. Histological grade of the cancer has consistently been associated with the risk of recurrence.
This study investigated whether the risk of recurrence after treatment for grade 1 breast cancer is sufficiently low to justify the safe discharge of patients once they have completed their active treatment. The rate of LRR and contralateral breast cancer (CBC) as the first event during follow-up after treatment of operable breast cancer was evaluated for the different tumour grades, and compared with the risk of primary breast cancer in the general population.
Methods
A consecutive series of women with operable breast cancer was the basis for the study, and included women who had received primary treatment at the Guy's Hospital Breast Unit between 1990 and 1997, with tumour grade recorded, and who had a modified radical mastectomy (MRM) or breast-conserving treatment (BCT). The population was obtained from the unit's research database. Patients who had received preoperative chemotherapy were excluded.
The hospital records for women who had LRR or CBC as the first event (including those found to have metastases after staging investigations) were reviewed, noting clinical tumour size and nodal status at time of first presentation, method of detection (patient, doctor or mammography) and mammographic finding if applicable (contralateral cancer or ipsilateral recurrence after BCT). Sentinel node biopsy was not in practice at that time. Standard BCT was wide local excision with negative surgical margins, full axillary clearance and postoperative breast irradiation. MRM involved excision of the breast and all the lymph nodes of the ipsilateral axilla with preservation of pectoralis major and minor muscles. Radiotherapy was given to the chest wall after MRM when the cancer was 5 cm or more in diameter, and to the supraclavicular fossa if four or more lymph nodes were involved with metastatic disease.
Data on patients' treatment and follow-up status were obtained from the Guy's Research Unit database. During this period, women were routinely followed indefinitely after their initial treatment, with clinical examination (two to three times per year for the first 3 years and annually afterwards) and annual mammography. For the purposes of the study, LRR was defined as any relapse or second primary in the conserved breast (after lumpectomy), or recurrence on the chest wall (after mastectomy) or in the axilla or supraclavicular fossa after either treatment. CBC was defined as breast cancer diagnosed in the contralateral breast. Histopathological or cytological evidence was routinely required as verification of relapse. Follow-up was terminated at the end of July 2006.
Histological tumour grade was assigned according to the Bloom–Richardson system for breast cancer. In this, tubule formation, nuclear pleomorphism and number of mitoses are taken into account: a score of 5 or less indicates grade 1, 6 or 7 grade 2, and 8 or 9 grade 3 cancer. The same system was used throughout the study. The small number of infiltrating lobular cancers were included with grade 2 ductal carcinomas, as disease-free and overall survival have been shown to be similar in these two subtypes4.
Statistical analysis
The absolute risk of LRR or CBC was calculated by means of cumulative incidence5, here denoted as cumulative risk. In this estimation both LRR and CBC were considered as events, whereas deaths and the presence of metastases were considered as competing risks and further information was censored. Ten-year estimates for the cumulative risk of LRR or CBC with confidence limits were calculated for subgroups based on primary surgical treatment (BCT group or MRM group) and histological grade (1, 2 or 3). Gray's test6 was used to assess differences between the treatment groups, with P < 0·050 (two sided) taken to indicate statistical significance.
Results
The population included 1143 women treated for breast cancer; 650 had BCT and 493 MRM. Clinical and tumour characteristics are summarized in Table 1.
Table 1.
Characteristics of 1143 women treated for breast cancer
| Overall (n = 1143) | Grade 1 (n = 165) | Grade 2 (n = 511) | Grade 3 (n = 467) | |
|---|---|---|---|---|
| Mean (range) age (years) | 53·0 (26–84) | 55·3 (27–84) | 54·0 (29–75) | 50·9 (26–75) |
| Treatment | ||||
| MRM | 493 (43·1) | 50 (30·3) | 232 (45·4) | 211 (45·2) |
| BCT | 650 (56·9) | 115 (69·7) | 279 (54·6) | 256 (54·8) |
| Nodal status | ||||
| Negative | 529 (46·3) | 94 (57·0) | 229 (44·8) | 206 (44·1) |
| 1–3 positive nodes | 393 (34·4) | 54 (32·7) | 166 (32·5) | 173 (37·0) |
| ≥ 4 positive nodes | 221 (19·3) | 17 (10·3) | 116 (22·7) | 88 (18·8) |
| Clinical tumour size (mm) | ||||
| Mean | 26·8 | 20·6 | 26·6 | 29·2 |
| Median | 25 | 20 | 25 | 25 |
Values in parentheses are percentages unless indicated otherwise. MRM, modified radical mastectomy; BCT, breast-conserving treatment.
The women had follow-up for a median of 9·6 (mean 9·1) years; 646 reached the end of follow-up with no events, 106 had LRR as a first event, and 26 had CBC. One hundred and ninety-eight women had distant metastases and 167 died without evidence of relapse. The cumulative risk of LRR/CBC in each treatment group is shown in Fig. 1. The 10-year estimate of LRR/CBC for the BCT group was 0·13 (95 per cent c.i. 0·11 to 0·16) and that for the MRM group was 0·11 (0·09 to 0·14).
Fig. 1.
Cumulative risk of locoregional recurrence (LRR) or contralateral breast cancer (CBC) by type of surgical treatment. BCT, breast-conserving treatment; MRM, modified radical mastectomy. P = 0·134 (Gray's test)
The 10-year cumulative risk of LRR for all women was 0·10 (95 per cent c.i. 0·09 to 0·12) and that of CBC was 0·02 (0·01 to 0·03).
The 10-year cumulative risk of LRR or CBC by grade for both treatment groups combined was 0·03 (95 per cent c.i. 0·01 to 0·08), 0·12 (0·09 to 0·15) and 0·16 (0·13 to 0·20) for grade 1, 2 and 3 cancer respectively.
The type of treatment (BCT or MRM) was influenced by age at diagnosis and disease characteristics at presentation, and affected the type of adjuvant therapy. Thus, type of treatment was associated with risk of LRR or CBC, and consequently more detailed analyses were stratified on type of surgery.
Breast-conserving treatment group
The 650 women who had BCT were followed for a median of 9·6 years; 115 had grade 1, 279 grade 2 and 256 grade 3 breast cancer. Five women with LRR/CBC originally had grade 1 breast cancer, the earliest recurrence occurring 5 years after treatment. Two of these recurrences were in the ipsilateral and three in the contralateral breast; all were detectable by mammography.
The 10-year cumulative risk of LRR and CBC was 0·11 (95 per cent c.i. 0·09 to 0·14) and 0·03 (0·02 to 0·04) respectively.
The cumulative risk of LRR/CBC among the three grades of breast cancer is shown in Fig. 2a. The 10-year estimates were 0·05 (95 per cent c.i. 0·02 to 0·11), 0·14 (0·11 to 0·19) and 0·16 (0·12 to 0·22) respectively. The difference was statistically significant (Gray's test statistic = 13·2, P = 0·001).
Fig. 2.
Cumulative risk of locoregional recurrence (LRR) or contralateral breast cancer (CBC) according to breast cancer grade after a breast-conserving treatment and b modified radical mastectomy. aP = 0·001, bP = 0·002 (Gray's test)
Modified radical mastectomy group
Of the 493 patients treated with mastectomy, 50 had grade 1, 232 grade 2 and 211 grade 3 cancer. Median follow-up was 8·3 years. No LRR or CBC was observed in women with a grade 1 tumour.
For the whole group, the 10-year estimate for LRR was 0·10 (95 per cent c.i. 0·07 to 0·13) and that for CBC 0·01 (0·01 to 0·03).
The cumulative risk of LRR or CBC among the different histological grades at 10 years was 0, 0·09 (95 per cent c.i. 0·06 to 0·14) and 0·16 (0·12 to 0·22) for grades 1, 2 and 3 respectively. The difference was statistically significant (Gray's test statistic = 13·0, P = 0·002) (Fig. 2b).
Discussion
The value of routine follow-up after breast cancer treatment has been scrutinized since several reports suggested that early diagnosis of recurrence had no survival benefit2,3,7. Although this is true for distant recurrences, it may not be the case for locoregional relapse. It has been suggested that, at least, a subgroup of patients with local recurrence might benefit from early detection and treatment1. Treatment of local relapse that is still at an asymptomatic stage is associated with improved survival2,3. Only a fraction of the recurrences are picked up by the patients themselves8,9, so, for the rest, routine follow-up may be crucial.
The major findings of the present study were that grade I breast cancer rarely recurred locally; the few recurrences were all in the breast and detectable by mammography. Women with grade 1 breast cancer treated by mastectomy had a particularly low risk of LRR or CBC during follow-up. Indeed, the risk of LRR or CBC after treatment for grade 1 breast cancer was similar to the risk of primary breast cancer in the screened population in the UK. For the year 2004, Cancer Research UK calculated that the risk of breast cancer in the general population ranged from 269 to 358 per 100 000 person-years annually for the screened ages (50–70 years). In the present study, women with a grade 1 tumour had a risk of LRR or CBC of 285 (95 per cent c.i. 93 to 670) per 100 000 person-years.
Several studies have previously reported rates of LRR ranging from 0 to 7 per cent after 5–10 years of follow-up for grade 1 breast cancer. Relapse rates were low after either mastectomy or BCT10–16. Even when radiotherapy was not given routinely after lumpectomy (usually in the context of a randomized trial) grade I breast cancers recurred much less frequently than other grades17–23. In previous reviews24 the risk of recurrence following the treatment of operable breast cancer has generally ranged from 5 to 80 per cent, with LRR constituting between 15 and 30 per cent of all relapses. The present study adds to the above findings.
The majority of women in the present study with grade 1 tumour either had no nodal involvement (94 patients) or only one node involved (28 patients). However, of the 43 tumours with more than one positive axillary node, LRR was never the first event; of the two ipsilateral breast relapses, one had one affected node and the other had no nodal involvement at initial diagnosis. Women with metastatic disease as a first event would have benefited little from surveillance aimed at the early detection of LRR.
The rising incidence of breast cancer and the advances in its treatment have led to a significant increase in the number of survivors after treatment for breast cancer. With finite resources, clinics could be targeting patients with a higher risk of relapse25, and breast cancer follow-up could be individualized26.
Most clinicians still favour follow-up, but there is no agreement on its length or intensity. The British Association of Surgical Oncology has suggested that women should be followed for 5 years27, whereas the American Society of Clinical Oncology recommends indefinite follow-up28. The National Institute for Health and Clinical Excellence, with its remit to consider health economics, has recommended a compromise of 3-year follow-up29. Some institutions have adopted an early discharge policy with immediate effect after completion of chemotherapy or radiotherapy25,30,31.
Although making strategic decisions based on only one tumour characteristic may be regarded as an oversimplification, this study suggests that women who have completed treatment for grade 1 breast cancer could be discharged from hospital follow-up, receive their adjuvant hormonal therapy from their general practitioner, and join a national screening or mammographic surveillance programme. At Guy's Hospital this would have reduced the follow-up load by 14·5 per cent.
Acknowledgements
The authors thank Dr Robin Wilson, Consultant Radiologist, Guy's Hospital, London, UK, for his support and suggestions.
L.H. and H.G. are funded by Cancer Research UK. The authors declare no conflict of interest.
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