Evaluation of Local and Systemic Disease Control Following Breast Conserving Surgery After Neoadjuvant Anastrozole Treatment
Sahni S, Daltrey I, Renshaw L, Miller WR, Dixon JM

Anastrozole is a one of the new generation of non-steroidal aromatase inhibitors. In clinical trials it has been demonstrated that when used as second line endocrine treatment for advanced breast cancer 1 mg of anastrozole is more effective than megestrol acetate with a survival advantage in favour of anastrozole. In the first line metastatic setting anastrozole is associated with a survival advantage over tamoxifen in ER positive patients. The Edinburgh Breast Unit has also studied anastrozole used as neoadjuvant treatment in postmenopausal women with hormone sensitive breast cancers.

To investigate the outcome of patients treated by neoadjuvant anastrozole with particular emphasis on local disease control in patients who initially would have required mastectomy but who after primary anastrozole treatment were suitable for breast conserving treatment.

• 26 postmenopausal patients were entered into the study
  
  
• 13 were randomised to receive a 1mg dose of anastrozole and 13 received a 10mg dose

Patient Details are summarised in Table 1

• Patients were treated with anastrozole for 3 months.
  
  
• Tumour size and volume was monitored by monthly clinical and ultrasound measurements and by mammography performed before and after the 3 month treatment period

Patients were enrolled in the study from March 1997 to June 1998.

• Response was calculated using three-dimensional volume and actual changes in tumour volume were calculated for clinical, ultrasound and mammographic measurements.
  
  

• Responses as assessed by changes in tumour volume measured clinically, mammographically and on ultrasound are shown in Table 2.

Click on images below for larger image view in new window:

Figure 2A	Figure 2B
Figure 2C	Figure 3

• Examples of a mammographic response and changes on ultrasound during treatment are shown in figures 2A, B, and C.
  
  
• An example of a clinical response is shown in Figure 3. The ulcerated area over the cancer are epithelialised during the three month treatment period.
  
  Summary of the Response data is presented in Table 2, Figure 4 and Figure 5.

Surgical Outcome

The numbers of patients who would have required mastectomy at the outset of treatment and the number of patients receiving treatment after 3 months anastrozole therapy is shown in Table 3. Axillary Surgery was undertaken in all patients.

• All patients who had breast conserving surgery had complete tumour     excision.

• 10 patients were histologically node positive.

  Treatment after surgery

• All patients who had breast conserving surgery also had post operative radiotherapy.
  

The patient with the locally advanced breast cancer shown in Figure 6 is shown following completion of her local therapy. 3 patients Ð all had 3 or more involved axillary nodes All patients were continued on 1mg of anastrozole, the plan being to continue this for 5 years		Click on image below for larger    image view in new window:
		Figure 6

All patients have been carefully monitored by regular clinical examination and yearly mammography.

Recurrences

• There has been 1 spot local recurrence 18 months post treatment treated by reexcision followed by a change in endocrine therapy from anastrozole to tamoxifen.

• There have been no systemic recurrences at a mean follow up period of 31 months.

• 3 patients complained of individual side effects which included night sweats 24 months after starting adjuvant anastrozole weight gain (1) and diarrhoea (1) 18 months after starting adjuvant anastrozole . None of these side effects were severe but in an effort to alleviate these symptoms all 3 patients were switched to tamoxifen with some amelioration of symptoms.

   

• Neoadjuvant anastrozole produces dramatic reductions in tumour volume over a 3 month period in postmenopausal patients with ER rich breast cancers. n Neoadjuvant anastrozole increases significantly the number of patients with large operable or locally advanced breast cancers who can be treated by breast con serving surgery.
  
  
• Local and systemic control of disease in this elderly group of patients with large or locally advanced breast cancers has been excellent with only a single local recurrence.
  
  
• Adjuvant anastrozole appears well tolerated and is likely to have contributed to the excellent disease free and overall survival of this group of patients.

   

• The use of neoadjuvant endocrine therapy followed by breast conserving treatment appears a reasonable option for postmenopausal patients with ER rich large operable or locally advanced breast cancer.
  
  
• Further evaluation of the role of anastrozole as neoadjuvant therapy in postmenopausal women is indicated.