Moving to a High-tech Approach to the Irradiation of Early Breast Cancer: Is It Possible to Balance Efficacy,Morbidity and Resource Use?

There is substantial evidence documenting the potential morbidity associated with radiotherapy in early breast cancer. An appraisal of current standard radiation practice is therefore necessary, given that women are surviving longer, have an improved quality of life, and are overcoming subsequent side-effects caused by postoperative irradiation. New technology allows the application of more complex approaches. This discussion paper considers some of the benefits of the widespread use of new complex approaches, such as intensity-modulated radiotherapy (IMRT) in the light of staffing and equipment shortfalls, and possible consequences on waiting times for treatment. The discussion is considered under the following themes: (1) which women with breast cancer benefit from complex treatment approaches? (2) What is the role of treatment accuracy in limiting morbidity? And (3) what is the potential effect of complex breast irradiation approaches on service delivery? In the UK, and globally, many departments are struggling to meet waiting-time guidelines. The use of more complex approaches for breast irradiation may increase this difficulty. However, a number of simple technical changes can be used to enhance efficacy and reduce levels of normal tissue morbidity. A sub-set of women who are at greatest risk from normal tissue morbidity or reduced cosmesis should be accurately defined in order to allow departments to plan their treatment strategies with optimal use of resources.     

Delaying Radiotherapy for the Delivery of Adjuvant Chemotherapy in the Combined Modality Treatment of Early Breast Cancer: Is It Disadvantageous and Could Combined Treatment be the Answer?

Women with early stage breast cancer are increasingly being treated with both adjuvant chemotherapy and radiotherapy. The optimal sequence of these two treatment modalities is yet to be defined. It remains controversial whether delaying radiotherapy in order to deliver chemotherapy compromises local disease control and survival. Consequently, clinical practice in the UK is divided, with a number of different combination schedules being used in an effort to bring forward the start of radiotherapy. In practice, however, any benefit in local control must be balanced against a potential increase in toxicity. A review of the current literature on the effect of radiotherapy delay is presented, together with data on the toxicity of combined chemo-radiotherapy schedules and recent data from clinical trials designed to determine the optimal sequencing of chemotherapy and radiotherapy.     

Is It Important to Adapt Neoadjuvant Chemotherapy to the Visible Clinical Response? An Open Randomized Phase II Study Comparing Response-Guided and Standard Treatments in HER2-Negative Operable Breast Cancer

Background.

Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment.

Methods.

Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m², respectively, for 3 cycles) followed by docetaxel (100 mg/m² for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed.

Results.

Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses.

Conclusion.

Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.     

In the Era After the European Organisation for Research and Treatment of Cancer ‘Boost’ Study,is the Additional Radiotherapy to the Breast Tumour Bed Still Beneficial for Young Women?

AimsThe European Organisation for Research and Treatment of Cancer (EORTC) 22,881–10,882 trial showed significant benefit of a radiotherapy boost (RTB) in women ≤40 years in a pre-hormone therapy (HT) era. We determined how the use of HT and RTB changed in response to clinical guidelines and whether the benefit of routine RTB was still observed in the HT era.Materials and methodsBetween 1996 and 2004, a provincial database identified all women ≤40 years with breast cancer who met the inclusion criteria of the EORTC trial. In total, 411 patients were classified into three eras defined by the guidelines: era 1 (discretionary HT, discretionary RTB); era 2 (routine HT, discretionary RTB); era 3 (routine HT, routine RTB). HT use, RTB use and cumulative incidence of local recurrence were calculated and compared across eras.ResultsHT use increased after the first policy change from 13% to 75% for oestrogen receptor-positive patients (P < 0.01). RTB use also increased from 33% to 76% following the second policy change (P < 0.01). At 10 years, the cumulative incidence of local recurrence was 12% in era 1, 6% in era 2 and 6% in era 3 (era 2 versus era 3, P = 0.92). For patients in the routine HT era (eras 2 and 3 combined) there was no significant difference in local recurrence between RTB and ‘no RTB’ patients (6% versus 7%, P = 0.81).ConclusionsThe routine use of HT and RTB increased significantly after new practice guidelines. Introduction of the HT guideline was associated with a 6% improvement in local recurrence at 10 years. No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. The routine use of a boost in unselected young women with negative margins should be re-evaluated in the current HT era.