Ductal Carcinoma In Situ of the Breast: One Reason for Considering Radiotherapy as Part of Breast-Conservation Therapy

Professor Silverstein urges us to consider treatment with excision alone for patients with ductal carcinoma in situ (DCIS). As a result of mammographic screening, DCIS now represents up to a quarter of all screen-detected cancers. When we were designing the randomized trials of treatment for DCIS in the 1980s at the time that mammographic screening was being introduced, we had predicted this epidemic and hoped to be able to establish whether there was a role for radiotherapy after wide excision [1]. Although we succeeded in demonstrating that radiotherapy reduced both local recurrence of DCIS and progression to invasive cancer, we were unsuccessful in convincing the oncological community that this modality should form part of breast-conserving surgery.

No such problem occurred with the management of invasive cancer treated conservatively. In the randomized trials of breast conservation that compared radiotherapy with no radiotherapy, breast relapse developed in 9–40% of nonirradiated cases [2–5]. No group could be identified as being at very low risk of relapse if not treated with radiotherapy. Despite there being no impact on mortality, radiotherapy has become accepted as an intrinsic part of breast-conserving therapy for invasive disease.

Why has this not happened after the publication of several trials demonstrating the benefit of radiotherapy after wide excision [6–9]? As Professor Silverstein points out, 35% of all DCIS patients in the Surveillance Epidemiology and End Results (SEER) 2003 database were treated with excision alone and, thus, substantial numbers of surgeons are not sending patients for radiation oncology evaluation. There are various possible explanations. Surgeons, who act as gatekeepers in the management of DCIS, either do not believe the data from the randomized trials or choose to ignore it. Is this the last bastion of surgical independence in the management of noninvasive breast cancer, all other areas having surrendered to the onslaught of radiation and medical oncologists? Could it be that there is a surgical misconception of the risk/benefits of breast irradiation?

A total of 11 reasons for eschewing radiotherapy have been put forward.

1. The fact that more than a third of cases are treated by excision alone is not a justification for the continuation of this approach. We would still be accepting the use of radical mastectomy for the management of stage I/II cancers if this was the case. Unfortunately, there has been little recent improvement in use of radiotherapy. In a North Carolina Cancer Registry study investigating 1893 patients with DCIS between 1998 and 1999, only 48% of those having breast-conserving surgery had postoperative irradiation [10]. The message is certainly not achieving universal penetration.

2. The ductal anatomy of the breast is not something that can be delineated by the surgeon, hence, the blunderbuss approach of quadrantectomy. Complete excision of DCIS will cure some patients but, most particularly, those that benefit have more extensive disease so that extirpation means a mastectomy.

3. Different grades of DCIS proliferate at different rates, but even among those with low-grade lesions, after long-term follow-up, 39% developed invasive disease [11]. Hence, grade alone cannot be used to select patients who will not benefit from radiotherapy.

4. Specialist breast pathologists whose services are available to general pathologists for problem cases are able to distinguish between atypical ductal hyperplasia and DCIS based on the extent of changes present. When borderline lesions are present, it is generally accepted that these patients should not be irradiated but, instead, should be observed.

5. The aim of primary treatment is to maximize the likelihood of local control and prevent progression to invasive disease, and this will not be achieved if radiotherapy is withheld.

6. Changes in radiotherapy delivery mean that potential damage to heart and lungs is now minimized.

7. Radiation-induced fibrosis may mask development of invasive disease, but the likelihood of that happening has already been reduced by 50% in those patients.

8. Although the ratio of invasive: DCIS may be greater in those receiving breast irradiation, the absolute numbers in the latter group are substantially lower. As an example, in the UK DCIS trial the ratios were 68:29 without radiotherapy and 9:6 after irradiation [8]. A meta-analysis of randomized trials comparing breast-conserving treatment for invasive cancer indicated that radiotherapy prevented one breast cancer-related death after breast cancer relapse, but this effect did not manifest until 15 years after treatment [12]. This predicted 2% survival benefit is also likely to be observed in those pateints with DCIS who have had breast irradiation.

9. As above, although radiotherapy makes subsequent breast reconstruction more challenging, this procedure will be used less frequently because of the cancers prevented by radiotherapy.

10. The randomized trials have not identified any subgroup of patients with DCIS who do not benefit from postoperative radiotherapy. Most recently, the Swedish trial group reported 8-year results with 64 ipsilateral recurrences in the irradiated group and 121 in the control group [13]. When patients were stratified by age, extent of DCIS, focality, completeness of excision and method of detection, no group could be identified that had a low risk without radiotherapy. The group concluded: “Further search with conventional clinical variables for a low-risk group that does not need radiotherapy does not seem fruitful.”

11. Political infighting in National committees may result in compromised recommendations for the management of DCIS that are not based on available evidence. This is hardly a cause for rejoicing.

Conclusion

Selecting treatment for patients with DCIS can be challenging, but it is important that the first treatment should be the best on offer. Undertreatment will lead to more recurrences, both DCIS and invasive, which are not only very distressing for the patient but may also lead to a worsening of prognosis since up to 20% of those patients will die of metastatic breast cancer [14]. Faced with such facts, many women will opt for the relative safety of breast irradiation after complete excision of DCIS.