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Aromatase activity in normal, benign, and malignant human breast tissues [Poster 44]
POSTER
AROHATASE ACTIVITY [Poster 441
PRESENTATIONS
IN NORUAL,l3ENIGN,ANDMALIGNANTIiUHANB~TTISSUES
J. C. Kouyoumdjian, F. Feuilhade, J. Beaune, and J. C. Rymer Laboratoire de Cancerologie Clinique et Fondamentale de l'universite, Paris Val de Marne, H8pital Henri Mondor, 94000 Creteil, France Estradiol is the major hormone that supports the growth of breast neoplasms. Recent data suggest that this steroid may be synthesized in situ by human breast tumors from androstenedione via aromatasr However, the clinical significance of this local estrogen production is not yet clearly demonstrated since most investigators agree that aromatase activity and estradiol receptor content are not correlated; only a minority show a positive correlation (1). On the other hand, in a preliminary report, Miller (2) has shown that the determination of estradiol biosynthesis in breast tissue may help select patients for treatment with aminoglutethimide (AG)(Orimetene, Ciba Geigy), whereas tumors without aromatase activity are unlikely to respond to such therapy. We have shown that benign tumors sometimes contain high levels of estradiol and progesterone receptors (ER and PR) comparable to cancers (3). However, the concentration of aromatase in these benign tumors is not known. In our study we have determined the level of aromatase activity in four groups of women prior to treatment: Group Group Group Group
1: 2: 3: 4:
normal breast tissues benign mastopathies, adenofibrosis, and fibrocystic mastosis adenocarcinomas metastatic cells mostly from pleural effusions
The levels of ER and PR were measured in same samples. Different clinical parameters were also determined, such as SBR histoprognostic grading. Aromatase activity in samples was determined according to the method of Rabe et al (4). Our data show a great variation in aromatase activity level from sample to sample in each group and also between differential groups (see Table 1). In normal cells (Group 1) aromatase activity was low (l/4). In benign tumors (Group 2) the level of estradiol biosynthesis is also low but greater than in normal cells (4/10). In adenocarcinomas (Group 3) 50% of tumors exhibited aromatase activity. In this group no correlation was observed between aromatase activity and receptor status or SBR grading. In groups 3 and 4 some patients are presently being treated with AG. A correlation between tumor aromatase and treatment efficiency was observed.
STEROIDS 50 /‘4-6 1987
639
640
Table
POSTER
1.
PRESENTATIONS
Correlation of Parameters. Patient
Aromatase Activity
ER
PR
Group 1
H.M. C.A. il. C.A.
+
63 40 (10
17 26 19 (10
Group 2
D.L. L.O. B.M. D.C. B.D. D.V. M.E. a. P. R.
+
74 58 27
i10
(10
(10
28
25 152 116 il 173 129 (10 60 183 19
38 74 36 i10 25 17 14 83 208 (10 i10 19
(10
(10 ;.6 (10 19 15
29 115 2025
(10 34 15
Group 3
A.G. C.J. L.M. L.M. N.E. S.A. C.M. A.M. R. N.J. R.S. C.M. IM. L.S. B.A. A.M. P.M. E.M.
Group 4
B.E. D.M. G.E. D.
+
+ +
+
+ +
SBR (grading)
II II III I I III III III II
Orimetene Treatment
(2,2,2j (2,3,lj (3,3,3j (1,2,lj (2,3,3)
PR NR
(3,3,1) (2,2,3)
NR
NR PR NR NR
REEXRENCES: i. Edery M, Goussard J, Dehennin L, Scholler R, Reiffsteck J, and Drosdowsky MA (1981). EUR J CANCER 17:115-120. 2. Miller WR and Forrest APM (1986). 14th INT CANCER CONGRESS, Budapest, Hungary (Abstr). 3. Kouyoumdjian JC, Feuilhade F, Pinaudeau Y, and Rymer JC (1986). BULL CANCER (PARIS) 73:120-123. 4. Rabe T, Rabe D, Bierwirth AM, and Runnebaum B (1982). J STEROID BIOCHEM 17:305-309.
STEROIDS
50 / 4-6 1987
AROHATASE ACTIVITY [Poster 441
PRESENTATIONS
IN NORUAL,l3ENIGN,ANDMALIGNANTIiUHANB~TTISSUES
J. C. Kouyoumdjian, F. Feuilhade, J. Beaune, and J. C. Rymer Laboratoire de Cancerologie Clinique et Fondamentale de l'universite, Paris Val de Marne, H8pital Henri Mondor, 94000 Creteil, France Estradiol is the major hormone that supports the growth of breast neoplasms. Recent data suggest that this steroid may be synthesized in situ by human breast tumors from androstenedione via aromatasr However, the clinical significance of this local estrogen production is not yet clearly demonstrated since most investigators agree that aromatase activity and estradiol receptor content are not correlated; only a minority show a positive correlation (1). On the other hand, in a preliminary report, Miller (2) has shown that the determination of estradiol biosynthesis in breast tissue may help select patients for treatment with aminoglutethimide (AG)(Orimetene, Ciba Geigy), whereas tumors without aromatase activity are unlikely to respond to such therapy. We have shown that benign tumors sometimes contain high levels of estradiol and progesterone receptors (ER and PR) comparable to cancers (3). However, the concentration of aromatase in these benign tumors is not known. In our study we have determined the level of aromatase activity in four groups of women prior to treatment: Group Group Group Group
1: 2: 3: 4:
normal breast tissues benign mastopathies, adenofibrosis, and fibrocystic mastosis adenocarcinomas metastatic cells mostly from pleural effusions
The levels of ER and PR were measured in same samples. Different clinical parameters were also determined, such as SBR histoprognostic grading. Aromatase activity in samples was determined according to the method of Rabe et al (4). Our data show a great variation in aromatase activity level from sample to sample in each group and also between differential groups (see Table 1). In normal cells (Group 1) aromatase activity was low (l/4). In benign tumors (Group 2) the level of estradiol biosynthesis is also low but greater than in normal cells (4/10). In adenocarcinomas (Group 3) 50% of tumors exhibited aromatase activity. In this group no correlation was observed between aromatase activity and receptor status or SBR grading. In groups 3 and 4 some patients are presently being treated with AG. A correlation between tumor aromatase and treatment efficiency was observed.
STEROIDS 50 /‘4-6 1987
639
640
Table
POSTER
1.
PRESENTATIONS
Correlation of Parameters. Patient
Aromatase Activity
ER
PR
Group 1
H.M. C.A. il. C.A.
+
63 40 (10
17 26 19 (10
Group 2
D.L. L.O. B.M. D.C. B.D. D.V. M.E. a. P. R.
+
74 58 27
i10
(10
(10
28
25 152 116 il 173 129 (10 60 183 19
38 74 36 i10 25 17 14 83 208 (10 i10 19
(10
(10 ;.6 (10 19 15
29 115 2025
(10 34 15
Group 3
A.G. C.J. L.M. L.M. N.E. S.A. C.M. A.M. R. N.J. R.S. C.M. IM. L.S. B.A. A.M. P.M. E.M.
Group 4
B.E. D.M. G.E. D.
+
+ +
+
+ +
SBR (grading)
II II III I I III III III II
Orimetene Treatment
(2,2,2j (2,3,lj (3,3,3j (1,2,lj (2,3,3)
PR NR
(3,3,1) (2,2,3)
NR
NR PR NR NR
REEXRENCES: i. Edery M, Goussard J, Dehennin L, Scholler R, Reiffsteck J, and Drosdowsky MA (1981). EUR J CANCER 17:115-120. 2. Miller WR and Forrest APM (1986). 14th INT CANCER CONGRESS, Budapest, Hungary (Abstr). 3. Kouyoumdjian JC, Feuilhade F, Pinaudeau Y, and Rymer JC (1986). BULL CANCER (PARIS) 73:120-123. 4. Rabe T, Rabe D, Bierwirth AM, and Runnebaum B (1982). J STEROID BIOCHEM 17:305-309.
STEROIDS
50 / 4-6 1987