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May 24, 1982 - Journal ofthe Royal Society ofMedicine Volume 75 September 1982 719. Variability ... between primary breast cancer and nodal metastases: preliminary .... Brennan M J, Donegan W L & Appleby D E (1979) American Journal of Cancer 137, 260-262 ... Jensen E V (1975) Cancer Research 35, 3362-3364.
Journal of the Royal Society of Medicine Volume 75 September 1982 719

Variability of oestrogen and progesterone receptor status between primary breast cancer and nodal metastases: preliminary communication Dolores Fernandez MSc Jamshid Alaghband-Zadeh mRcpath

Paul Sauven FRCS J Ian Burn FRCS

Charing Cross Hospital, Fulham Palace Road, London W6 8RF

Summary: The synchronous relationship between oestrogen (ER) and progesterone (PgR) receptor status in primary tumours and their nodal metastases has been analysed in 26 patients. All patients with ER-negative primary tumours were found to have ER-negative axillary nodes but of those with ER-positive tumours only 65% had, correspondingly, all nodes ER-positive. The concentration of ER in the nodes was found to be significantly lower (P< 0.001) than that in the primary tumour. PgR information was unobtainable in 3 patients. Of the remainder, 75O% of those having PgR-negative tumours had all nodes PgR-negative but only 36% of those with PgR-positive tumours had all nodes PgRpositive. PgR levels were found to be generally lower in the axillary nodes but this did not reach statistical significance. The clinical relevance of these findings is discussed. Introduction The first observation on the hormonal control of breast cancer was made by Beatson in 1896 when he reported the regression of two breast cancers in premenopausal women following oophorectomy. It was not until 1971 that Jensen identified cytoplasmic oestrogen receptors, and subsequently demonstrated the association between the presence of receptor in tumour tissue and endocrine responsiveness (Jensen et al. 1971, Jensen 1975). McGuire et al. (1977) demonstrated the induction of progesterone receptor, following the binding of a cytosol oestrogen receptor, and its subsequent translocation and binding as a nuclear oestrogen receptor (Figure l). They suggested that the presence of progesterone NUCLEUS

CYFOPLASM

G

~~~~~~~~~~~~~~~E

R RE

c

-

E

RE

-

N

~~~~~~N M

RPc Expression of Oestrogen Response

R=Receptor EsOestrogen P=Progesterone

Figure 1. Sequence of events following binding of oestrogen to its receptor

receptor might be an indication of a more functionally intact receptor system, and that measurement of progesterone receptor would therefore be a more accurate predictor of subsequent endocrine responsiveness than measurement of oestrogen receptor alone. More recently, the oestrogen receptor status of primary breast tumour has been correlated with disease-free interval following surgical treatment, and this prognostic information is 1 Based on paper read to Section of Surgery, 3 March 1982. Accepted 24 May 1982

0141-0768/82/090719-04/$01.00/0

(C-) 1982 The Royal Society of Medicine

720 Journal of the Royal Society

of Medicine

Volume 75 September 1982

independent of that gained from lymph node status, age, menopausal status and size and location of tumour (Hahnel 1981). In the.present study the levels of oestrogen and progesterone receptors found in the primary tumours have been compared with those found in the axillary lymph nodes in a group of patients undergoing mastectomy. Methods Eighty-one early breast carcinomas treated by mastectomy had a careful nodal dissection of the mastectomy specimen performed and any three nodes considered to be macroscopically invaded were bisected. One half was used for receptor assays, and the other for histopathology and an estimate of cellularity. All remaining nodes were labelled and sent for histology only. Oestrogen (ER) and progesterone (PgR) receptor levels were analysed in the primary tumours (obtained at biopsy), and subsequently in one to three lymph nodes, after invasion had been confirmed histologically. Oestrogen and progesterone receptor levels were assayed by the Dextran Coated Charcoal method as described by King et al. (1979). A level of 5.0 fmol/mg cytosolic protein or above was taken as positive. Results Of 81 mastectomy specimens analysed, 55 had only non-invaded lymph nodes. Receptor studies were performed in 12 of these and in all cases non-invaded nodes were found to be negative for ER and PgR. The remaining 26 patients had one or more invaded nodes analysed (Table 1). Of 17 patients with ER-positive (ER+) primaries, 11 had solely ER+ nodes, a 65% consistency. All 9 ERnegative (ER-) primaries had ER - nodes (I 00% consistency), and the overall consistency was thus 770. Table 1. Oestrogen (ER) and progesterone (PgR) receptor status in primary breast cancer and nodal metastases Progesterone receptor status

Oestrogen receptor status

Patients

Primary

Nodal

Patients

Primary

Nodal

26

17 ER+

11 ER+ 2 ER+ and ER- (mixed) 4 ER-

23

11 PgR+

4 PgR+

9 ER-

9 ER-

2 PgR+ and PgR- (mixed) 5 PgR12 PgR-

9 PgR3 PgR- and PgR+ (mixed)

In 3 patients there was insufficient nodal tissue to assay progesterone status; nodes from the remaining 23 patients were therefore analysed (Table 1). Of 11 PgR-positive (PgR+) primaries only 4 had all nodes PgR+, a consistency of 36%. However, 9 of the 12 PgRnegative (PgR -) tumours had all nodes PgR - (75%o-consistency). The overall consistency was

57%o.

The levels of ER were found to be-significantly lower in the axillary metastases than in the primary tumours (Figure 2). This statistical significance was not altered when a correction was made for cellularity. In most patients PgR was also lower in the nodal metastases although this did not reach statistical significance. Discussion Many authors have me'asured serial ER levels in primaries and in subsequent metastases, usually with treatment in the interval, and they report a wide variation in ER levels (Webster et al. 1978, Singhakowinta et al. 1976). Four authors have included simultaneous biopsies

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a

*XX ER TUMOUR