Natural History Of Breast Cancer Research Articles

Results of treatment of stage I–III breast cancer in Black Americans. The Cook County Hospital experience, 1973-1987

Whether the prognosis for black women with breast cancer differs from that of nonblack women remains controversial. The treatment results of 526 black women who received definitive therapy for Stage I-III breast cancer at Cook County Hospital, 1973 through 1987 are presented. The 5-year and 10-year projected survival rates for 272 node-negative patients (83.9% and 76.6%, respectively) and for 72 node-positive nonadjuvant treated patients (58.1% and 35.2%, respectively) are similar to those reported in the literature for nonblack patients. Adjuvant therapy improved the projected relapse-free (P = 0.0744) and overall survival curves (P = 0.0448) for 182 node-positive patients compared with nonadjuvant patients. The greatest benefit was seen for patients greater than 50 years of age with one to three positive nodes. The incidence of estrogen and progesterone receptors was found to be similar to those reported for nonblack patients. Once breast cancer has been diagnosed and appropriately treated, there appear to be few differences in the natural history of breast cancer between black and nonblack patients.

Natural History of Breast Cancer

The natural history of breast cancer has been, and will be, extremely hard to study. Indirect evidence suggests that any cancer cell population may be phenotypically unique with multiple abnormal traits which decisively forge the clinical behavior. Histopathologic grouping will only give a very imperfect reflection of phenotypical individuality. It is proposed that essential determinants of the subsequent behavior have already been fixed during the induction period, i.e. long before the clinical debut. This may to some extent be reflected by the DNA content of the tumor cells. Metastases to axillary lymph nodes is strongly determined by size of primary tumor according to a function which suggests a smooth linear risk for lymphatic spread over a broad size interval. It is suggested that each cell of any given cancer may be endowed with a small chance of dissemination to axillary lymph nodes which may be essentially constant during the entire natural life history. Number of cancer cells of the primary tumor would then be the decisive determinant for risk of metastatic dissemination. It is not necessary to invoke qualitative progression from 'non-metastasibility' to 'metastasibility'. Small differences exist in the natural history of different histological types of breast cancer.

Chapter I. Biology and natural history of breast cancer

Chapter I. Biology and natural history of breast cancer

Primary localized breast cancer

As understanding of the natural history of breast cancer has increased, radical mastectomy has given way to a preference for breast-sparing surgery and greater reliance on radiation therapy and chemotherapy. Probably the most important factor for selection of treatment is consultation with a multidisciplinary team skilled in the various procedures and techniques that might be efficacious. The key to successful management is selection of an appropriate course of treatment with which the patient feels comfortable.

Radiotherapy in Non-small Cell Lung Cancer: An Overview

First, in NSCL, as in all other cancers, postoperative RT can have an impact on survival only in patients without occult metastases at the time of initial treatment and in whom residual tumor has been left by the surgeon. This subset of patients ought to be limited, because if the tumor is small, the surgeon will be able to resect it completely; if it is large and has spread along the lymphatic pathways, resection is difficult and there is a high likelihood of distant dissemination. The natural history of breast cancer is fairly well quantitated, and it was estimated that for breast cancer the subset of patients who can benefit from postoperative radiotherapy is not larger than approximately 20% of patients.

The biology and natural history of breast cancer from the screening perspective.

A review of the tumor biology of breast cancer from the screening perspective reveals important research issues. It is not known if the induction phase includes any detectable preneoplastic lesions. Evidence for the existence of preneoplasias is conflicting. The effect of removal of such lesions on the incidence of breast cancer has not yet been studied. The mechanisms that govern progression of in situ lesions--or even small preclinical invasive cancers--are not fully understood. It is not clear to what extent progression into cancers with metastatic behavior occurs. Current predictors for progression are weak. One major benefit of the scientific evaluation of the screening programs is that we can learn more about the natural history of the disease. Mammographic screening detects tumors that are smaller in size than those detected by clinical examination only. There is an inverse relationship between tumor size and the probability that the patient has acquired axillary metastases. These facts, taken together, indicate that the mortality reduction seen in screening is a result of a real impact on the natural history. Calculations of the lead time gained in randomized screening projects give empirical proof that a third of the cancers progress from a localized stage to a disseminated disease relatively late in the preclinical phase of the tumor. Analyses of interval cancers in screening have pointed to the conclusion that the net growth rate of the primary tumor does not directly parallel metastatic ability, and that the tumors grow faster in younger women.

Sex hormone-binding globulin and the natural history of breast cancer.

Low concentrations of SHBG in the blood appear to be related to rapid tumour growth rates whereas normal values are associated with slower rates. The inferences drawn from these and other experimental results are as follows: 1. It is no longer necessary to postulate that an abnormal endocrine environment is related to the risk of breast cancer. 2. Variation within the normal range of endocrine function may be sufficient to account for marked differences in the growth rates of transformed cells. 3. It is suggested that women whose tumours arise in an environment characterised by SHBG concentrations at the lower end of the normal range (and, hence, non-SHBG-bound oestradiol levels at the top end of the range) will tend to have an earlier age at diagnosis, a lower frequency of oestrogen-receptor positive tumours and a lower proportion of hormone responsive tumours than women with SHBG levels at the top of the range. 4. Case/control studies in which growth rates are not taken into account may be difficult to interpret.

An overview and critical analysis of breast cancer screening.

From October 1973 through September 1979, 10,000 women were screened for breast cancer as part of a national project. In this follow-up analysis, we evaluate the current status of 166 women whose tumors were detected by this screening project (women with bilateral malignant neoplasms have been excluded). Mammogram abnormalities only were present in 55 women and abnormal physical findings with or without an abnormal mammogram were present in 111 women. Overall, 75% of patients were diagnosed with stage I (n = 86) or stage II (n = 39) disease. Median follow-up was 117 months. Only eight women (14.5%) whose tumors were detected by mammogram have suffered a relapse. Recurrences have developed in 27 women (24.3%) in the group with abnormal physical findings with or without an abnormal mammogram. Disease-free and relative survival at ten years' follow-up are 79.6% and 83.7%, respectively, for the 166 women whose cancer was detected by mammography only and by physical examination with or without an abnormal mammogram. Further follow-up will be required to determine the impact of screening detection on the natural history of breast cancer.

Breast Cancer and its Management

The cosmetic surgeon should be aware of the natural history of breast cancer, the method for diagnosis, and alternatives of treatment. Diagnosis can be made prior to or during a cosmetic breast procedure, usually at a time when the neoplasm is highly curable.

Cell kinetics, growth rate and the natural history of breast cancer. The Heuson Memorial Lecture

Cell kinetics, growth rate and the natural history of breast cancer. The Heuson Memorial Lecture

The relation between survival and age at diagnosis in breast cancer.

We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.

Consensus conference. Adjuvant chemotherapy for breast cancer

In 1985, breast cancer will be diagnosed in approximately 120,000 women; in 90% of these women, the disease will apparently be limited to the breast and axillary lymph nodes. Despite advances in early diagnosis and primary treatment with surgery, radiation therapy, or both, more than a third of these patients will develop systemic disease and ultimately die. In the broadest sense, all of these patients are potential candidates for some form of systemic adjuvant therapy. Adjuvant therapy of breast cancer involves the use of cytotoxic drugs or endocrine therapy after definitive primary therapy. The rationale is to eradicate occult metastatic disease that otherwise would be fatal. The goal of adjuvant therapy is to significantly prolong survival, while maintaining an acceptable quality of life. Three measures are important in evaluating whether this goal is met by specific treatments: 1. The effect of therapy on overall survival: the length of time a woman survives following a diagnosis of breast cancer. 2. The effect of therapy on disease-free survival: the length of time a woman remains free of any recurrence of disease. Prolonged periods of disease-free survival may be advantageous in their own right, since quality of life is likely to be better before than after relapse. There is also some evidence that longer periods of disease-free survival may translate into better overall survival rates. 3. The effect of therapy on quality of life: in choosing an adjuvant therapy program, potential benefits must be balanced against both short-term and long-term side effects. Also important are the substantial psychological, social, and economic problems women may experience as a result of treatment. An increasing number of important prognostic variables have been identified that define the natural history of breast cancer. These include well-established factors such as histological status of axillary lymph nodes, primary tumor size, steroid hormone receptors, menopausal status or age, and histopathology. Assessment of cell differentiation and proliferation, which can be determined by newer techniques, may also be significant. The pathological status of the axillary lymph nodes remains the single most important prognostic variable, and four lymph node categories have been defined (negative, one to three positive nodes, four to nine positive nodes, and ten or more positive nodes). Since definitions of menopausal status vary widely among clinical trials, age (less than 50 vs greater than or equal to 50 years) can be substituted as a prognostic variable.(ABSTRACT TRUNCATED AT 400 WORDS)

A contribution to the natural history of breast cancer. V. Bilateral primary breast cancer: incidence, risks and diagnosis of simultaneous primary cancer in the opposite breast.

Tissue from contralateral breast was taken from 505 patients with invasive breast cancer. Every 5th patient had simultaneous carcinoma in the opposite breast, 7.7% (39/505) had invasive cancer, and 13.1% (66/505) had carcinoma in situ. Invasive cancers in the opposite breast were diagnosed at an earlier stage as compared with the neoplasm of the primary breast. However, 26% of the patients already had positive axillary nodes. The following risk indicators of the bilateral disease were found: age at time of diagnosis, histologic type of tumours, familial breast cancer, suspicious mammography, P2/DY-breast parenchymal pattern (Wolfe) and multicentric cancer of primary breast. Our findings support the proposal to consider bilaterality of breast cancer as a sign of systemic disease of the breasts, involving the ductal and lobular system within eight quadrants of a paired organ (Ober).

Long-term survival in 406 males with breast cancer.

Survival was analyzed during a follow-up period of up to 20 years in 406 (97%) of all 420 males in whom breast cancer was diagnosed in Sweden in 1960-1978. After correction for the expected mortality in the general population, cumulated survival rates (with 95% confidence limits) of 66 (58.7-72.5)% and 52 (42.0-62.1)% at 5 and 10 years respectively were found. These figures and the general pattern of relative survival rates were in close accordance with those noted in a concomitant series of female breast cancer. There was a trend toward slightly improved survival rates during the period of study and the median survival times were 3.9, 4.8 and 7.2 years for patients diagnosed in 1960-64, 1965-69 and 1970-74 respectively. Age at diagnosis was seemingly unrelated to the long-term relative survival. We conclude that, except for a slightly higher mean age at diagnosis in males, there is a striking similarity in the natural history of breast cancer between men and women after initial treatment, with an excess death rate which still persists at long-term observation.

To the Editor.-Reply

—As mentioned in our article, the exact dose and dose fractions were not known on the majority of patients as these treatments were not administered at our institute. The objective of this study was to evaluate the natural history of breast cancer in patients with prior radiation exposure. The question about ionizing radiation resulting in an increased incidence of breast cancer during the developmental phase has been previously addressed by number of publications, and that was not the objective of our study. The article did not contain any statement trying to induce fear of ionizing radiation. The only suggestion that was made was that patients with a history of ionizing radiation should be followed up closely to detect the disease in its earlier stage. I do not believe that was a disservice to the public. The comments of Forman et al are valid in that the article did not

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and a low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

Breast cancer, genetics, and age at first pregnancy.

Hereditary breast cancer shows a distinctive natural history characterised by an earlier age of onset, excess bilaterality, vertical transmission, heterogeneous tumour associations, and improved survival when compared to its sporadic counterpart. To date, very little attention has been given to interrelationships between breast cancer risk factors and genetics. In the general population, early age of first term pregnancy has been generally accepted as protective against breast cancer. In addition, recent findings suggest that an early age of first pregnancy may be associated with an earlier age of breast cancer diagnosis. We studied the age at first pregnancy and age at onset of breast cancer among 162 females at 50% genetic risk, 72 of whom had already developed the disease. We then compared them to 154 consecutively ascertained breast cancer patients from the Creighton Cancer Center. In the hereditary subset (1) early first term pregnancy did not alter the frequency of breast cancer; (2) early age at first term pregnancy was not associated with an earlier age at cancer diagnosis; and (3) age of breast cancer onset in nulliparous females was not significantly lower than that in females having at least one term pregnancy. We speculate, therefore, that in our hereditary population, pregnancy does not influence the natural history of breast cancer in the same way that it does in the population at large.

A contribution to the natural history of breast cancer. III. Changes in the basement membranes in breast cancers with stromal microinvasion.

Twenty-eight small breast cancers and 17 other breast cancer specimens from which appropriate semi-thin sections had been prepared were examined by electron microscopy and special staining techniques for alterations in the basement membranes and the basal lamina. In each case disruptions of the basement membranes were invariably observed at the point of initial invasion. Two types of invasion were noted: (1) bud-like protrusions of intraduct cancer with disruption of the basement membranes at the point of invasion; (2) extensive basement membrane defects with single cancer cell invasion. Our study confirms that invasive breast cancer originates in intraductal or lobular carcinoma in situ.

A contribution to the natural history of breast cancer. II. Precursors and lesions associated with small cancers of the breast.

Breast duct obliteration and periductal elastosis were studied in 100 breast carcinomas with a maximum diameter of 20 mm or less. Seventy percent of all tumours and 90% of lobular and tubular carcinomas had obliterated ducts with radial scars at the centre of the lesion. Obesity, parity and diabetes mellitus had no apparent association with duct obliteration and periductal elastosis. The striking two peaks in age distribution suggest the presence of endocrine influences. Duct obliteration with periductal elastosis occurs where the breast shows most changes during development and involution making this the high risk zone for carcinogenesis.

A contribution to the natural history of breast cancer. IV. Lobular carcinoma in situ and its relation to breast cancer.

We studied 52 patients with lobular carcinoma in situ (LCIS) of the breast, tissue being available from both breasts in 46 patients. Detailed histological examination of the tissue was combined with specimen radiography. By this technique, six invasive cancers were detected within 2 years of the primary diagnosis. five of these six carcinomas were clinically occult and were not suspected at specimen radiography. Three other invasive cancers were discovered 4 years, 7 years, and 10 years after diagnosing LCIS. The extent of the LCIS in the primary biopsy was the only feature which gave a guide to the possible presence and location of an occult invasive lesion.