Aromatase Inhibitors and Treatment of Breast Cancer

Neoadjuvant protocols in which therapy is given with the primary cancer remaining within the breast allow tumor responses to be assessed in individual patients by monitoring changes in tumor volume during treatment. Impressive anti-tumor effects have been observed in selected groups of patients with estrogen receptor (ER)-a rich cancers. (19, 35) (Table 2). Marked reduction in tumor size provides clinical benefits, and many patients who initially required mastectomy or were inoperable can be treated by more conservative breast surgery (19, 35) (Table 3).

Table 2. Median Tumor Volume Reduction in Series of Patients with Locally Advanced BC who Received Neoadjuvant Endocrine Therapy in the Edinburgh Breast Unit1

Patients

Patients with <

Patients

Number

with > 50%

50% Reduction or

with >25%

Agent

of

Reduction,

<25% Increase,

Increase,

Patients

n(%)

n (%)

n(%)

Letrozole

36

32 (89)

3(8)

1(3)

Anastrozole

23

18(78)

5(13)

0

Exemestane

12

10(83)

2(17)

0

1 Tumor volume changes assessed by ultrasound during the 3.0-mo treatment period.

1 Tumor volume changes assessed by ultrasound during the 3.0-mo treatment period.

Table 3. Patients with Locally Advanced BC Requiring Mastectomy Before and After Neoadjuvant Endocrine Therapy in the Edinburgh Breast Unit

Number

Number

Number

Initially

Requiring

Conversion

Agent

of

Requiring

Mastectomy

Rate, %'

Patients

Mastectomy

After Treatment

Letrozole

36

24

2

93

Anastrozole

242

19

2

89

Exemestane

12

10

2

80

1 Percentage of patients initially considered only for mastectomy that underwent breast-conserving surgery following treatment.

1 Percentage of patients initially considered only for mastectomy that underwent breast-conserving surgery following treatment.

Includes one patient who did not complete full treatment.

Effects on tumor morphology and histopathology may also be monitored by examining sequential biopsies before and during neoadjuvant therapy (36, 37). The latest generation of aromatase inhibitors is capable of producing marked changes in tumor morphology; clear reductions in cellularity/increases in fibrosis are observed in most tumors following treatment (38, 39).

Therapy with aromatase inhibitors also produce a marked and consistent reduction in the proportion of tumor cells staining positively with the Mib1 antibody, a useful surrogate marker for proliferative activity (40). Similarly, following treatment, staining for progesterone receptors (PR), a marker of E response, are significantly reduced (often to zero) in over 90% ofthe tumors studied (40). These results are consistent with anti-estrogen and anti-tumor effects of aromatase inhibitors.

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