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HISTOLOGICAL GRADE AND RESPONSE TO ENDOCRINE THERAPY IN BREAST CANCER
101 ASSOCIATION BETWEEN HISTOLOGICAL GRADE OF INFILTRATING DUCT CARCINOMA AND THE RESPONSE OF ADVANCED DISEASE TO ENDOCRINE THERAPY
Xtest with 2 df p
1.
oestrogens, androgens, or tamoxifen. The response to treatment was assessed using criteria recommended by the UICC.2 The association between response to therapy and histological grade is given in the table. The response rate in patients with grade I (100%) is significantly higher than in those with grade 11 (40%) and
grade in (21%) tumours. Effect of drying and/or storage
on
the
immunological reactivity
of
HAVAg.
NaN=sodium azide.
chimpanzee stool had no effect on the SPRIA response for HAVAg within the 15-day storage period. The linear response of the diluted untreated control in the SPRIA for HAVAg (see figure) will simplify quantitative determinations of HAVAg in future studies of antigen stability after exposure to other physical or chemical stresses
or
in
epidemiological investigations
to
identify
contaminated inanimate surfaces. We have demonstrated that HAVAg in a stool suspension remains immunologically reactive after 15 days of storage at 25°C in both liquid and dried states. This does not mean that HAV infectivity will survive a similar treatment; the question of virus stability can be answered only by post-treatment inoculation of either tissue culture
susceptible laboratory primates. If, however, a particular physical or chemical stress is subsequently found to inactivate the immunological reactivity of HAVAg, we feel there is a high probability that HAV infectivity will also be destroyed. or
Hepatitis Laboratories Division is a World Health Organisation Collaborating Centre for Reference and Research on Viral Hepatitis.
These results show that patients with well-differentiated infiltrating duct carcinomas are more likely to respond to endocrine therapy than are patients with poorly differentiated tumours. This association is not widely recognised, although a small series of cases described by Huggins and Daosupports this finding. More detailed analysis will show the relative interdependence between histological grade and other prognostic variables, such as
disease-free interval, steroid receptor status, and tumour elastosis. Nevertheless, the findings strongly support the suggestion that histological grading of breast tumours could assist in the development of a useful index for predicting response to endocrine
therapy. Imperial Cancer Research Fund, Breast Cancer Unit,
London SE1 9RT
R. R. MILLIS R. D. RUBENS
Department of Pathology, Institute of Urology, St Paul’s Hospital, London
J. R. W. MASTERS
Department of Radiotherapy, Guy’s Hospital
M. J. MINTON
Guy’s Hospital,
ENDOTOXINS AND THE HEPATORENAL SYNDROME
The
Hepatitis Laboratories Division, Center for Infectious Diseases, Centers for Disease Control, Phoenix, Arizona 85014, U.S.A.
W. W. BOND KAREN A. MCCAUSTLAND D. W. BRADLEY
HISTOLOGICAL GRADE AND RESPONSE TO ENDOCRINE THERAPY IN BREAST CANCER
SIR,-Response of advanced breast cancer to endocrine therapy is predictable, and correlates with features such as long postoperative disease-free interval and the presence of steroid receptor activity and elastosis within the tumour. These features are interrelated and seen more commonly in well-differentiated than in anaplastic tumours, and therefore it might be expected that better differentiated tumours would be more likely to respond to endocrine therapy. We have data in support of this hypothesis. A consecutive series of patients with progressive locally advanced and/or disseminated breast cancer, receiving endocrine therapy as first systemic treatment, was studied. In 192 cases the primary tumour was an infiltrating duct carcinoma and could therefore be graded histologically according to a system! which considers tubular differentiation, nuclear pleomorphism, and mitotic activity, and grades tumours as: i-well-differentiated, n-intermediate, or m-anaplastic. The endocrine therapy for premenopausal patients was ovarian ablation (either by surgical oophorectomy or by pelvic irradiation), while postmenopausal patients received either to some extent
1 Bloom HJG, Richardson WW. Histological grading and prognosis J Cancer 1957, 11: 359-77.
in breast cancer. Br
SIR,-The nephropathy that develops in patients with liver cirrhosis may present clinically as anything from latent renal insufficiency to irreversible renal failure, and it is characterised pathophysiologically by decreased renal perfusion secondary to vasoconstriction.4-6 As Dr Bercoff and colleagues state (May 16, p. 1097) the role of endotoxaemia in this renal vasoconstriction remains controversial; and in cirrhotics with renal hypoperfusion but without overt renal failure it is doubtful if endotoxaemia has a causative role.7-9 In 35 cirrhotic patients without overt renal failure mean renal blood flow (MRBF) and cortical blood flow (CBF) were measured by xenon-133 washout. 10 The normal range was set as the mean±2 2.
Hayward JL, Carbone PP, Heuson J-C, Kumaoka S, Segaloff A, Rubens RD. Assessment of response to therapy in advanced breast cancer. Eur J Cancer 1977; 13: 89-94.
Huggins C, Dao
TL-Y. Adrenalectomy and oophorectomy in treatment of advanced of the breast. JAMA 1953; 151: 1388-94. 4. Tristani FE, Cohn JN. Systemic and renal hemodynamics in oliguric hepatic failure: Effect of volume expansion. J. Clin. Invest. 1967; 46: 1894. 5. Epstein M, Berk D, Hollenberg NK, Adams DP, Chalmers TC, Abrams HL, Merril JP. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. 3.
carcinoma
Am J Med 1970; 49: 175. 6. Kew MC, Brunt PW, Varma RR, Hourigan KJ, Williams HS, Sherlock S. Renal and intrarenal blood flow in cirrhosis of the liver. Lancet 1971; ii: 504. 7. Wilkinson SP, Williams R. Endotoxins and renal failure in liver diseases. In: Bartoli E, Chiandussi L, eds. Hepato-renal syndrome. Padua: Piccin Medical Books, 1979: 229-56. 8. Wilkinson SP, Portman B, Hurst D, Williams R. Pathogenesis of renal failure in cirrhosis and fulminant hepatic failure. Postgrad Med J 1975; 51: 503. 9. Clemente C, Bosch J, Rodés J, Arroyo V, Mas A. Marragal S. Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis. Gut 1977; 18: 556. 10. Merkel C, Gatta A, Zuin R, Milani L, Spina GP. Renal and intrarenal blood flow in patients with cirrhosis before and after portal-systemic shunt Scand J Gastroenterol 1980; 15: 389.
Xtest with 2 df p
1.
oestrogens, androgens, or tamoxifen. The response to treatment was assessed using criteria recommended by the UICC.2 The association between response to therapy and histological grade is given in the table. The response rate in patients with grade I (100%) is significantly higher than in those with grade 11 (40%) and
grade in (21%) tumours. Effect of drying and/or storage
on
the
immunological reactivity
of
HAVAg.
NaN=sodium azide.
chimpanzee stool had no effect on the SPRIA response for HAVAg within the 15-day storage period. The linear response of the diluted untreated control in the SPRIA for HAVAg (see figure) will simplify quantitative determinations of HAVAg in future studies of antigen stability after exposure to other physical or chemical stresses
or
in
epidemiological investigations
to
identify
contaminated inanimate surfaces. We have demonstrated that HAVAg in a stool suspension remains immunologically reactive after 15 days of storage at 25°C in both liquid and dried states. This does not mean that HAV infectivity will survive a similar treatment; the question of virus stability can be answered only by post-treatment inoculation of either tissue culture
susceptible laboratory primates. If, however, a particular physical or chemical stress is subsequently found to inactivate the immunological reactivity of HAVAg, we feel there is a high probability that HAV infectivity will also be destroyed. or
Hepatitis Laboratories Division is a World Health Organisation Collaborating Centre for Reference and Research on Viral Hepatitis.
These results show that patients with well-differentiated infiltrating duct carcinomas are more likely to respond to endocrine therapy than are patients with poorly differentiated tumours. This association is not widely recognised, although a small series of cases described by Huggins and Daosupports this finding. More detailed analysis will show the relative interdependence between histological grade and other prognostic variables, such as
disease-free interval, steroid receptor status, and tumour elastosis. Nevertheless, the findings strongly support the suggestion that histological grading of breast tumours could assist in the development of a useful index for predicting response to endocrine
therapy. Imperial Cancer Research Fund, Breast Cancer Unit,
London SE1 9RT
R. R. MILLIS R. D. RUBENS
Department of Pathology, Institute of Urology, St Paul’s Hospital, London
J. R. W. MASTERS
Department of Radiotherapy, Guy’s Hospital
M. J. MINTON
Guy’s Hospital,
ENDOTOXINS AND THE HEPATORENAL SYNDROME
The
Hepatitis Laboratories Division, Center for Infectious Diseases, Centers for Disease Control, Phoenix, Arizona 85014, U.S.A.
W. W. BOND KAREN A. MCCAUSTLAND D. W. BRADLEY
HISTOLOGICAL GRADE AND RESPONSE TO ENDOCRINE THERAPY IN BREAST CANCER
SIR,-Response of advanced breast cancer to endocrine therapy is predictable, and correlates with features such as long postoperative disease-free interval and the presence of steroid receptor activity and elastosis within the tumour. These features are interrelated and seen more commonly in well-differentiated than in anaplastic tumours, and therefore it might be expected that better differentiated tumours would be more likely to respond to endocrine therapy. We have data in support of this hypothesis. A consecutive series of patients with progressive locally advanced and/or disseminated breast cancer, receiving endocrine therapy as first systemic treatment, was studied. In 192 cases the primary tumour was an infiltrating duct carcinoma and could therefore be graded histologically according to a system! which considers tubular differentiation, nuclear pleomorphism, and mitotic activity, and grades tumours as: i-well-differentiated, n-intermediate, or m-anaplastic. The endocrine therapy for premenopausal patients was ovarian ablation (either by surgical oophorectomy or by pelvic irradiation), while postmenopausal patients received either to some extent
1 Bloom HJG, Richardson WW. Histological grading and prognosis J Cancer 1957, 11: 359-77.
in breast cancer. Br
SIR,-The nephropathy that develops in patients with liver cirrhosis may present clinically as anything from latent renal insufficiency to irreversible renal failure, and it is characterised pathophysiologically by decreased renal perfusion secondary to vasoconstriction.4-6 As Dr Bercoff and colleagues state (May 16, p. 1097) the role of endotoxaemia in this renal vasoconstriction remains controversial; and in cirrhotics with renal hypoperfusion but without overt renal failure it is doubtful if endotoxaemia has a causative role.7-9 In 35 cirrhotic patients without overt renal failure mean renal blood flow (MRBF) and cortical blood flow (CBF) were measured by xenon-133 washout. 10 The normal range was set as the mean±2 2.
Hayward JL, Carbone PP, Heuson J-C, Kumaoka S, Segaloff A, Rubens RD. Assessment of response to therapy in advanced breast cancer. Eur J Cancer 1977; 13: 89-94.
Huggins C, Dao
TL-Y. Adrenalectomy and oophorectomy in treatment of advanced of the breast. JAMA 1953; 151: 1388-94. 4. Tristani FE, Cohn JN. Systemic and renal hemodynamics in oliguric hepatic failure: Effect of volume expansion. J. Clin. Invest. 1967; 46: 1894. 5. Epstein M, Berk D, Hollenberg NK, Adams DP, Chalmers TC, Abrams HL, Merril JP. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. 3.
carcinoma
Am J Med 1970; 49: 175. 6. Kew MC, Brunt PW, Varma RR, Hourigan KJ, Williams HS, Sherlock S. Renal and intrarenal blood flow in cirrhosis of the liver. Lancet 1971; ii: 504. 7. Wilkinson SP, Williams R. Endotoxins and renal failure in liver diseases. In: Bartoli E, Chiandussi L, eds. Hepato-renal syndrome. Padua: Piccin Medical Books, 1979: 229-56. 8. Wilkinson SP, Portman B, Hurst D, Williams R. Pathogenesis of renal failure in cirrhosis and fulminant hepatic failure. Postgrad Med J 1975; 51: 503. 9. Clemente C, Bosch J, Rodés J, Arroyo V, Mas A. Marragal S. Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis. Gut 1977; 18: 556. 10. Merkel C, Gatta A, Zuin R, Milani L, Spina GP. Renal and intrarenal blood flow in patients with cirrhosis before and after portal-systemic shunt Scand J Gastroenterol 1980; 15: 389.