Growth rate and natural history of breast cancer]

Available data on growth rate of human breast cancers and their kinetic of cell proliferation were reviewed. Breast cancers are among those human cancers with the longest doubling time and the lowest labelling index, however the spread of the individual values is especially large. Analysis of the data indicate that half of the metastases began to grow more than about two years before the time when the primary tumor reached a clinically detectable size. The prognostic influence of the delay between the time when the tumor reached a clinically detectable size and the treatment is discussed. A correlation is observed between the growth rate of the primary tumors and the mean survival of the deceased patients. This is probably due to correlation between the growth rates of the primary and of the metastases. The growth rate of the primary seems to have little influence, if any, on the probability of metastatic dissemination per tumor cell. This probability varies widely among various clinical types of breast tumors and is probably correlated with other parameters such as the presence of an inflammatory reaction.     

The natural history of breast cancer: implications for a screening strategy

In the data base of the Institut Gustave-Roussy, the clinical courses of over 7000 patients treated since 1951 are registered. For 3000 of them treated prior to the introduction of adjuvant chemotherapy, the follow-up ranges from 15 to 32 years. For all patients, the size of the primary tumor, its histologic grade, and the number of involved axillary nodes at the time of initial treatment were registered prospectively. This series of patients was used to analyze the relationship between the size of the primary tumor and the probability of distant metastatic spread, taking into account other prognostic variables. A simulation model of the natural history of breast cancer was built which satisfactorily fits the available data on breast cancer screening. The aim of this paper is to use this model to assess the influence of: a) the time interval between mammographies and b) the diagnostic ability of the screening program, on the proportion of patients with distant metastases. The results show that the proportion of patients with distant metastases at the time of diagnosis increases gradually from approximately 25% for an interval of 1 year to 40% for an interval of 5 years. Moreover, the proportion of patients with metastases is critically influenced by the size of the tumors which can be detected; for example, for a 2-year interval the proportion of patients with metastases increases from 32% for tumors screened of 1 cm in diameter to 40% for tumors of 1.7 cm in diameter.     

Care pathway of women with interval breast cancer in 2016, based on medico-administrative data

BackgroundSince 2004, an organised screening programme (OS) for breast cancer has been in place for 50-74 years women who are not at an increased risk. Despite this, 17% of cancers diagnosed within 24 months following an OS mammogram are interval cancers (IC), diagnosed even though the OS had not reported cancer. After identifying IC from the French administrative healthcare database (SNDS), our objective was to describe the care pathways of women with IC in 2016.Materials and MethodsThe IC identification algorithm is based on breast imaging tests conducted in the 24 months prior to diagnosis and on the compatibility of their timeline with ACR3 lesion follow-up (BIRADS guidelines). The care pathways of 3 groups were compared: women with IC, diagnosed through the OS, and diagnosed outside the OS programme (personalised screening or based on clinical signs, PSCS group).ResultsRespectively, 12,965 (46%), 3433 (12%), and 11,761 women (42%) were classified in the OS, IC and PSCS groups, i.e. 20.9% IC cases among the women taking part in the OS programme. The women from the IC group presented with more forms with lymph node or metastatic involvement than those of the OS group. Their pathways were more complex than in the OS group: at an equivalent stage, more total mastectomies and more adjuvant or neoadjuvant chemotherapy regimens.ConclusionThe care pathways of women with IC are intermediate with respect to those of the OS or PSCS group.Cases of IC probably include several cancer prognosis profiles.     

Development and use of a natural history data base of breast cancer studies

Pretreatment information, type of treatment, and longitudinal follow-up on 1,971 patients with operable breast cancer were used to establish a breast cancer natural history data base (NHDB). Data were available for 957 patients with stage I (node-negative) breast cancer and 1,014 stage II (node-positive) patients. In women with negative nodes, information was available on 759 patients treated at the Milan National Cancer Institute and 188 patients treated at the Royal Marsden Hospital. After adjustment for differences in the distribution of patient prognostic factors, relapse-free survival and overall survival were not significantly different. Of the 1,014 node-positive patients, 540 were treated at the Milan National Cancer Institute, 258 at the Royal Marsden, and 216 at the M. D. Anderson Hospital. Relapse-free survival and overall survival did not significantly differ between Milan patients and those treated at the Royal Marsden Hospital. However, M. D. Anderson Hospital patients did have significantly better relapse-free and overall survival. In each institution, outcome was consistently most dependent on the number of involved axillary lymph nodes and tumor size. Also, similar patterns of survival were observed for each of the institutions. The development of an NHDB can be of value in the identification and evaluation of consistency of prognostic factors, permitting improved comparisons between clinical trials. The development of such a natural history data base (NHDB) provides a reference for assessing the impact of different adjuvant chemotherapy programs, and aids in the design of new protocols.     

Inferring the natural time history of breast cancer: Implications for tumor growth rate and early detection

Summary This review analyzes the results of 692 breast cancer patients from the Norwegian Radium Hospital. All cases were diagnosed during the period 1951–1959 and the average follow-up time was just under eight years. All patients received a radical mastectomy and had their diagnoses pathologically confirmed by a separate reviewer. The purpose of this paper is to apply a novel method of analysis in order to infer the longitudinal course of the disease as if it had not been interrupted by treatment. The method allows one to estimate the average times between changes in the biological factors which characterize the natural history of the disease. Applying this method to the Norwegian data has resulted in identifying three pathways of the natural history of the disease. The tumor growth rates differ for these pathways and are in the approximate ratio 1:5:27. Furthermore, we can estimate the potential benefit from earlier diagnosis. Two of the three pathways would seem to benefit from earlier detection.     

Age-specific interval breast cancers in Japan: estimation of the proper sensitivity of screening using a population-based cancer registry

The age-specific sensitivity of a screening program was investigated using a population-based cancer registry as a source of false-negative cancer cases. A population-based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population-based cancer registry to estimate the number of false-negative cases of screening program. Among 112 071 women screened by mammography combined with CBE, the number of detected cancers, false-negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false-negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population-based cancer registry was much lower than that in women 50-59 and 60-69 years of age (40-49: 18, 71.4%, 50-59: 19, 85.8%, 60-69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population-based cancer registry for detecting false-negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age.     

Effect of organized mammography screening on breast cancer mortality: A population-based cohort study in Norway

We aimed to estimate the effect of organized mammography screening on incidence-based breast cancer mortality by comparing changes in mortality among women eligible for screening to concurrent changes in younger and older ineligible women. In a county-wise balanced, open-cohort study, we used birth cohorts (1896–1982) to construct three age groups in both the historical and screening period: women eligible for screening, and younger or older women ineligible for screening. We included women diagnosed with breast cancer who died within the same age-period group during 1987–2010 (n = 4,903). We estimated relative incidence-based mortality rate ratios (relative MRR) comparing temporal changes in eligible women to concurrent changes in ineligible women. Additionally, we conducted analyses comparing the change in eligible women to younger, ineligible women with either continued accrual and follow-up period (eligible women only) or continued follow-up period. All three age groups experienced a reduction in mortality, but the decrease among eligible women was about the same among ineligible women (relative MRR = 1.05, 95% CI: (0.94–1.18)). Varying the definition of follow-up yielded similar results. Mammography screening was not associated with a larger breast cancer mortality reduction in women eligible relative to ineligible women.     

Health beliefs, salience of breast cancer family history, and involvement with breast cancer issues: adherence to annual mammography screening recommendations

Involvement in breast cancer (BC) issues, and the degree to which family history of BC influences perceived risk (salience of family history), have been proposed as additions to the Health Belief Model as applied to mammography adherence. Barriers and benefits of mammography, perceived susceptibility, severity, cues to action, salience of family history, and issue involvement with respect to BC were examined in adherent (n=97) and non-adherent (n=213) women. Adherent women with positive family histories reported greater benefits of mammography, greater response to cues to action, and higher salience of family history than women with negative family histories. Non-adherent women with positive family histories reported fewer benefits of mammography and greater issue involvement, and perceived BC as less severe than those with negative family histories. Benefits (OR=1.51), susceptibility (OR=1.41), issue involvement (OR=1.59), severity (OR=0.66), and cues to action (OR=0.75) were significantly associated with adherence. Results have implications for evidence-based interventions.     

What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial.

Further results are presented from the Swedish two-county breast cancer screening trial. The reduction in the rate of advanced cancers and of breast cancer mortality in the group allocated to screening when compared to the control group has accelerated with a further year of follow-up. Mortality due to other causes and the rate of other cancers remains similar in the two groups. Attention has been focused on the rate at which cancers start re-emerging among women with negative mammograms. Among women over 50 years of age at entry to the study, relatively few interval cancers are seen in the first two years after a screening test; in the third year the rate rises to nearly 50% of the comparable rate in the control group. Among women aged 40-49 years at entry, by contrast, the rate of interval cancers even in the first post screening year is nearly 40% of that in the controls and in the second year nearly 70%. In older women in the group allocated to screening, much of the breast cancer mortality comes from the refusers and little from the interval cancers; in younger women the picture is reversed. The implications for screening policy, including the interscreening interval are discussed.     

The natural history of breast carcinoma in the elderly: implications for screening and treatment

BACKGROUND: The authors evaluated the two indicators of metastatic proclivity (namely, virulence [V; the rate of appearance of distant metastases] and metastagenicity [M; the ultimate likelihood of developing distant metastases]) of breast carcinoma in elderly women. The authors then compared these characteristics with the corresponding characteristics in a cohort of younger women to determine whether breast carcinoma was more indolent in women age > 70 years, as is commonly believed in the medical community. METHODS: The authors examined 2136 women who underwent mastectomy without adjuvant systemic therapy at The University of Chicago Hospitals (Chicago, IL) between 1927 and 1987. The median follow-up period was 12.3 years. Distant disease-free survival (DDFS) was determined for women who did not receive systemic therapy. V and M were obtained from log-linear plots of DDFS. RESULTS: No significant difference in tumor size at presentation was observed among women age < 40 years, women ages 40-70 years, and women age > 70 years (P = 0.86), whereas significantly fewer women age > 70 years presented with positive lymph nodes compared with younger women (P = 0.05). In women with negative lymph node status, there was a higher DDFS rate among patients ages 40-70 years (81% at 10 years) compared with patients age > 70 years (65% at 10 years; P = 0.018). There was no significant age-related difference among women with lymph node-positive disease (P = 0.2). For example, the 10-year DDFS rate for women ages 40-70 years was 33%, compared with 38% for women age > 70 years. Among those with lymph node-negative disease, V was 3% per year for women ages 40-70 years as well as women age > 70 years. Among women with lymph node-negative disease, M was 0.20 for patients ages 40-70 years and 0.35 for patients age > 70 years. In women with positive lymph node status, both V (11% per year vs. 10% per year) and M (0.70 vs. 0.65) were similar in both age groups. CONCLUSIONS: Fewer women age > 70 years had lymph node involvement at presentation. However, when this finding was taken into account, the authors found no evidence that breast carcinoma was more indolent in women age > 70 years. These results support the use of similar diagnostic and therapeutic efforts for elderly women and younger women, with modification for elderly women based only on comorbidity.     

Natural history of human breast cancer: Recent data and clinical implications

Summary This study of the natural history of human breast cancer was based on the analysis of a series of 3000 patients treated by radical mastectomy at a single institution (Institut Gustave Roussy) at a time when adjuvant chemotherapy was not prescribed. The follow-up of the patients ranged from 15 to 30 years; for each patient the tumor size, the number of involved axillary nodes, and the histological grade were prospectively registered.A highly significant correlation was found between tumor size and the probability of distant metastatic dissemination. The distribution of tumor sizes at metastatic spread was log-normal with a median diameter equal to 3.5 cm.The patients were subdivided into 3 groups according to the histological grade. In each subgroup there was a significant correlation between tumor size and the probability of distant spread; the distributions were log-normal and the median size was markedly larger for grade 1 tumors. Moreover the proportion of grade 1 tumors was higher in small tumors than in large ones while the reverse was observed for grade 3 tumors; these data suggest that during their growth tumors progress towards higher grades.One of the chief fundamental characteristics of a tumor seems to be its propensity for axillary node invasion. The orderly pattern of nodal involvement makes it possible to calculate the tumor size at invasion of the first axillary node in each subset of patients. A strong and highly significant correlation exists between the size of the tumor at initation of distant metastasis and at invasion of the first lymph node. However the capacity for lymphatic spread is, on average, acquired much earlier than the capacity for metastatic spread.With a simple model based on these data it was possible to compute the proportion of patients with occult metastases as a function of tumor size, histological grade, and number of involved axillary nodes.Early invasion of axillary nodes is associated with a rapid growth rate of the primary tumor (or a high S-phase fraction). However each of these variables has an independent prognostic significance; the S-phase fraction appears as one of the strongest prognostic indicators.A model of tumor growth was used to assess the impact of screening procedures on the proportion of patients with distant metastases. The predictions of the model are consistent with the results of the screening programs. The model was used to predict the influence of the interval between mammographies on the proportion of patients with distant metastases and on the size of these metastases. Since the curability of distant metastases by adjuvant chemotherapy is, to a large extent, governed by their size, the model can predict the cumulative effect of screening procedures and adjuvant chemotherapy on the proportion of patients with overt distant metastases.     

Mean sojourn time, overdiagnosis, and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening

This study aimed to assess the mean sojourn time (MST) of prostate cancer, to estimate the probability of overdiagnosis, and to predict the potential reduction in advanced stage disease due to screening with PSA. The MST of prostate cancer was derived from detection rates at PSA prevalence testing in 43 842 men, aged 50–69 years, as part of the ProtecT study, from the incidence of non-screen-detected cases obtained from the English population-based cancer registry database, and from PSA sensitivity obtained from the medical literature. The relative reduction in advanced stage disease was derived from the expected and observed incidences of advanced stage prostate cancer. The age-specific MST for men aged 50–59 and 60–69 years were 11.3 and 12.6 years, respectively. Overdiagnosis estimates increased with age; 10–31% of the PSA-detected cases were estimated to be overdiagnosed. An interscreening interval of 2 years was predicted to result in 37 and 63% reduction in advanced stage disease in men 65–69 and 50–54 years, respectively. If the overdiagnosed cases were excluded, the estimated reductions were 9 and 54%, respectively. Thus, the benefit of screening in reducing advanced stage disease is limited by overdiagnosis, which is greater in older men.     

Phyllodes tumors of the breast: natural history, diagnosis, and treatment

Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a wide range of clinical behavior. These tumors are categorized as benign, borderline, or malignant based on a combination of histologic features. The prognosis of phyllodes tumors is favorable, with local recurrence occurring in approximately 15% of patients overall and distant recurrence in approximately 5% to 10% overall. Wide excision with a greater than 1 cm margin is definitive primary therapy. Adjuvant systemic therapy is of no proven value. Patients with locally recurrent disease should undergo wide excision of the recurrence with or without subsequent radiotherapy.     

Clinical characteristics and analysis of survival rate of breast cancer patients with a family history in Japan

We compared the clinical characteristics and survival rate of 52 patients of unilateral breast cancer with family history (UFH) with 665 patients with no family history (UNFH). The distribution of clinical stage and histologic type were almost equal between two groups. The estrogen receptor-positive rate was significantly higher in UFH than UNFH. As for a disease-free survival, there was no difference, however, the overall survival seemed to be better in UFH than in UNFH. These results suggest that the survival of the UFH may depend on a higher incidence of estrogen receptor-positive cases because UFH responds well to hormonal treatment after relapse.     

Steroid-hormone receptors in nonpalpable and more advanced stages of breast cancer. A contribution to the biology and natural history of carcinoma of the female breast

Tumors of five groups of patients, with (1) nonpalpable primary breast cancer, (2) palpable operable primary breast cancer, (3) loco-regionally advanced primary breast cancer, (4) first and (5) late metastatic breast cancer, were studied in respect to their steroid receptor content. A statistically significant decrease of progesterone receptor positive tumors and of tumors positive for estradiol and progesterone receptors, was found with increasing advance of the disease. A reversed extrapolation of these figures supports the hypothesis that every breast cancer contains steroid receptors and is hormone-dependent from its inception.     

Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study

Introduction  

The aims of this study were to determine trends in the incidence of advanced breast cancer at screening mammography and the potential of screening to reduce it.     

Impact of NHS breast screening on advanced disease and mortality from breast cancer in the North West of England

A cohort study was undertaken to describe outcomes from breast cancer in women who were aged 54 years or younger when they were first invited for NHS breast screening. The analysis included 5125 women invited for multiple rounds of breast screening by the Wigan screening programme and 10 750 women invited by the Manchester programme. The main outcome measures were rates of advanced disease and mortality from breast cancer. In Wigan 4028 (78.6%) and in Manchester 5485 (51.0%) women accepted all of their invitations for screening. The incidence of invasive cancer was higher in Wigan than in Manchester (24.78 vs 21.11 per 10 000 person-years; chi(2)=2.11, 1 df, P=0.15), but the rate of advanced disease was significantly lower (2.49 vs 4.73 per 10 000 person-years; chi(2)=4.36, 1 df, P=0.04). Mortality was lower in Wigan than in Manchester (2.46 vs 4.31 per 10 000 person-years; chi(2)=3.25, 1 df, P=0.07). In the first report of long-term outcomes in women invited for NHS breast screening, we demonstrated that it is possible to evaluate the impact of screening by comparing programmes with different proportions of regular attenders; a significant difference was shown in the rate of advanced disease between two programmes with different cancer detection and attendance rates.