The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative, 1 to 3, or greater than or equal to 4 positive nodes. Results, however, reveal that there is a risk in combining all patients with greater than or equal to 4 positive nodes into a single group. Since there was a 25% greater disease-free survival and an 18% greater survival in those with 4 to 6 than in those with greater than or equal to 13 positive axillary nodes, such a unification may provide misleading information regarding patient prognosis, as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population. Of particular interest were findings relating the conditional probability, i.e., the hazard rate, of a treatment failure or death each year during the 5-year period following operation to nodal involvement with tumor. Whereas the hazard rate for those with negative, or 1 to 3 positive nodes, was relatively low and constant, in those with greater than or equal to 4 positive nodes the risk in the early years was much greater, but by the fifth year it was similar to that occurring when 1-3 nodes were involved, and not much different from negative node patients. The same pattern existed whether 4 to 6 or greater than or equal to 13 nodes were positive. When the current findings are considered relative to other factors with predictive import, it is concluded that nodal status still remains the primary prognostic discriminant.

Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update.

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50 to 60 percent are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of clinical relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of Er and an assay for progesterone receptor (PgR) are two methods for increasing the accuracy of selecting or rejecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be a better marker of tumor hormone dependence than quantitative ER.

The value of estrogen and progesterone receptors in the treatment of breast cancer

Purpose: To determine whether progesterone receptor (PgR) status provides additional value to estrogen receptor (ER) status and improves prediction of benefit from endocrine treatment among patients with primary breast cancer. Patients and Methods: Clinical outcomes of patients in two large databases were analyzed as a function of steroid receptor status. The first database (PP), contained 3,739 patients who did not receive any systemic adjuvant therapy and 1,688 patients who received adjuvant endocrine therapy but no chemotherapy. The second database (SPORE), contained 10,444 patients who received adjuvant endocrine therapy but no chemotherapy. Biochemical ER and PgR assays were identically performed in two different central laboratories. Results: In univariate and multivariate analyses, the prognostic significance of PgR status among systemically untreated patients is modest. Among endocrine-treated patients, however, multivariate analyses, including lymph-node involvement, tumor size, and age, demonstr...

Progesterone Receptor Status Significantly Improves Outcome Prediction Over Estrogen Receptor Status Alone for Adjuvant Endocrine Therapy in Two Large Breast Cancer Databases

The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site

Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c- erbB -2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c- erbB -2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.

https://cancerres.aacrjournals.org/content/canres/49/8/2087.full.pdf

Expression of c-erbB-2 Oncoprotein: A Prognostic Indicator in Human Breast Cancer

This study was designed to determine whether the estrogen receptor (ER) status of a primary breast cancer has prognostic value and how this information compares with the information gained from lymph node status at masectomy 335 primary breast carcinomas were tested for ER in tumor cytosol fractions Of the 335 177 contained ER and 158 contained no significant amounts of ER; the respective percentages of ER positive and negative tumors were 528 and 472 151 patients experienced carcinoma spread to the regional lymph nodes (484%) and 161 had no detectable metastases (516%) There was no connection between lymph node status and receptor status The ER status was correlated with disease-free interval survival and site of recurrent disease ER positive carcinomas had a longer disease-free interval longer survival (calculated from time of mastectomy to death) and longer time interval between recurrence and death Lymph node status at mastectomy also influenced these parameters ER positive cancers had significantly better chance of survival independent of lymph node status ERs also delayed recurrence in lymph-node-positive carcinomas; this advantage deteriorated with increasing time from operation ER positive or negative primary carcinomas showed no predilection for spread to any particular site however The significant differences in this report were P < 01

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197908%2944%3A2%3C671%3A%3AAID-CNCR2820440238%3E3.0.CO%3B2-V

Prognostic value of estrogen receptors in primary breast cancer.

The steroid specificiy of the estrogen-receptor of human breast carcinoma

THE specificity of the Kober1,2 reaction for oestrogen assay has been studied as part of a general investigation of the mechanisms of steroid acid colour reactions. Exactly what constitutes a positive Kober reaction has never been denned; in this work, a Kober positive steroid is regarded as one which produces pink chromogen absorbing maximally in the 500–555 mµ region by the Brown3,4 or Ittrich5–Bradshaw6 procedures. This chromogen we have designated χ4 because at least three other chromogens absorbing at shorter wavelengths are produced by the Kober reaction with various oestrane derivatives. On this basis, from a study of 116 relevant steroids, the following features of the steroid molecule were found to be simultaneously necessary if the steroid is to give a positive Kober reaction. An oxygen function (carbonyl or hydroxyl) is essential at either C16 or C17 and is permissible at both. The only exceptions are the Δ16-steroid discussed later and 16-oxoestrone; oestroiie-16 is only feebly positive. Of the fifteen possible combinations of oxygen function at C16 and/or C17, thirteen have been tested and all except the two just mentioned are strongly positive and give a pink chromogen with emax of 30,000 to 60,000.

Specificity of the Kober reaction.

The quantitative relationship of urinary oestrogen conjugates after injection of tritiated oestradiol

the dissemination of information and advice is likely to have to proceed in a piecemeal fashion. Doctors and health workers can play a part. On occasions they will become aware that patients are engaging in unsafe sexual practices, and will be able to offer advice about changing to safer behaviour. It is imperative that health workers take as long as is required to counsel such patients about the risks to which they are exposing themselves and all their sexual (and illicit-drug-injecting) partners. The second major issue that arises from the unsafe sexual practices of men who do not identify with the homosexual community is the risk that they pose to their female partners (and their subsequent contacts) who are not aware of their high-risk activities, and thus may assume that sexual intercourse generally is safe. If we know little about \"beat users\", we know even less about their female partners. We suspect that most of them would not believe that their male partners could present such a risk to them, and would not be prepared to insist on the use of a condom because it might impute that their partners had, in fact, been engaging in unsafe sexual practices. In view of this context, the importance of specific educational efforts that are directed at women cannot be underestimated. In the current climate in Australia, where the incidence of HIV infection among heterosexual persons is low and most persons do not know heterosexual persons with HIV infection, it is easy to adopt the selfexempting belief that \"this sort of thing only happens to other people, not nice respectable and sensible people like me\". As experience in other campaigns has shown us, individuals can exempt themselves in the face of overwhelming evidence of personal risk,\" especially where a significant delay occurs between the risk-taking behaviour and the onset of symptoms. This clearly is the case for HIV infection, as it is for tobacco-related diseases, and for many other health-protective behaviours. Experience from these campaigns shows us that behavioural changes are likely to be slow. The changes that have occurred in the homosexual community in response to AIDS probably are larger than those that have been achieved for any other kind of risk-taking behaviour. We believethat the commitment of the homosexual community to behavioural change has been an important component of this massive change. We will need to see equivalent levels of commitment from the rest of the community if we are to prevent the further spread of HIV infection. These are grounds for concern that the widespread adoption of safer sexual practices purely to prevent exposure to HIV will not occur until members of a community feel at risk. In the interim, it may be useful to highlight existing risks, especially where protective measures overlap those for preventing HIV. For example, those sexual and needle-sharing practices which are \"safe\" in terms of the spread of HIV will at least reduce the spread of some diseases which currently are more prevalent among heterosexual persons, such as hepatitis B, chlamydial infection, syphilis and gonorrhoea. Frequently, consultations with doctors and other health workers will revolve around issues of sexuality (for example, sexually transmitted diseases or women who are undergoing regular cervical smear-tests), and in this context health workers can educate their patients about safer sexual practices, not only in terms of reducing the spread of HIV infection, but with reference to reducing that of all sexually transmitted diseases. Education is important in that it can facilitate broader changes in attitudes and behaviours which may encourage safer practices, either directly by way of changed beliefs about what is acceptable or desirable, or by way of the acceptance of, or lobbying for, environmental change. Some of the broader changes that are needed to prevent the spread of HIV include changing attitudes towards casual sexual activities, the eroticization of condoms and other safer sexual practices (for example, non-penetrative sexual activities) and, in the case of persons who inject illicit drugs, finding ways to discourage needleand syringe-sharing. Acknowledgements We thank Robyn Mullins, Rob Moodie and Ian Goller of the Health Promotion Unit, Health Department Victoria, for their comments on earlier drafts. RON BORLAND

Roland Hähnel

Papers

Prognostic value of estrogen receptors in primary breast cancer.

The steroid specificiy of the estrogen-receptor of human breast carcinoma

Specificity of the Kober reaction.

The quantitative relationship of urinary oestrogen conjugates after injection of tritiated oestradiol

Oestrogen receptors and prognosis in breast cancer.