Age as prognostic factor in premenopausal breast carcinoma

Rochefordière, Anne de la; Campana, F.; Fenton, J.; Vilcoq, J.R.; Fourquet, A.; Asselain, Bernard; Scholl, Suzy; Pouillart, P; Durand, Jean‐Claude; Magdelénat, H.

doi:10.1016/0140-6736(93)92407-k

Cited by 429 publications

(234 citation statements)

References 24 publications

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“…To our knowledge, no other oncogenic markers as predictors of locoregional recurrence have been identified previously. At present, the common risk factors for local control after breastconserving treatment are: patient age, margin status, and the presence of an extensive intraductal component (De la Rochefordiere et al, 1993;Elkhuizen et al, 1998;Voogd et al, 1999Voogd et al, , 2001). The addition of new predictive markers for locoregional recurrence may help in guiding the optimal type of local therapy.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

et al. 2004

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The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 nodenegative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients. The treatment of breast cancer is guided by risk factors. Approximately 70% of all node-negative breast cancer patients can be cured by locoregional therapy alone. This automatically implies that the remaining 30% of these patients will develop a recurrence despite adequate locoregional therapy. Currently, treatment strategy in breast cancer is based upon tumour stage, grade, and hormone receptor status. Additional prognostic factors are greatly needed, first to select those patients who might benefit from adjuvant systemic therapy and second to optimise locoregional therapy in order to avoid locoregional recurrences.The prognostic significance of a considerable number of tumour markers has already been investigated but to date, none of these factors can be used to guide the treatment of primary breast cancer.A recent study by Barlund et al (2000a) demonstrated that amplification of a putative tumour marker called P70 S6 kinase protein (PS6K) might be associated with poor outcome in breast cancer. In addition, the authors reported that RPS6KB1 gene amplification and PS6K overexpression are significantly correlated.The RPS6KB1 gene is located at 17q23 and amplified in approximately 10% of all primary breast cancer cases. PS6K is a ribosomal protein that is involved in the progression from the G1 to S phase of the cell cycle. It is rapidly activated in response to mitogenic stimuli, for example, growth factors, cytokines, and oncogene products (Grove et

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Section: Discussionmentioning

confidence: 99%

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

et al. 2004

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“…Taken together, however, patients Յ 35 years had a significantly worse survival than their older counterparts (36 -65 years, P ϭ 0.0003). In a multivariate analysis of data from the Institut Curie Paris, De La Rochefordiere et al suggested that age was an independent factor for predicting both survival and relapse, 22 but a similar analysis of patients treated at Guy's Hospital failed to show age as a significant independent variable, the significant variable being high grade, which was strongly associated with young age. 23 We did not detect a statistically significant difference in the incidence of Grade III cancers between the young and very young, but again there was definitive evidence that young women as a whole (Յ 35 years) have a much higher preponderance of high grade tumors (P ϭ 9 ϫ 10 Ϫ12 ).…”

Section: Discussionmentioning

confidence: 99%

Breast carcinoma in women age 25 years or less

Kothari

Beechey-Newman

D’Arrigo

et al. 2002

Cancer

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BACKGROUNDAlthough several studies have examined breast carcinoma in young women aged ≤ 35 years at diagnosis, there are only occasional cases reported in very young women aged ≤ 25 years, and, to the authors' knowledge, no series are available. The presentation, tumor biology, behavior, and outcome of breast carcinoma in very young women are not known, and the rarity of breast malignancy within this age group could lead to diagnostic delays.METHODSThe tumor characteristics and survival of 15 women aged ≤ 25 years at the time of diagnosis, have been reviewed and compared with women aged 26–35 years under the care of Guy's Hospital's Breast Unit during the same period of time. Where appropriate, the two groups were individually matched for tumor size (clinical measurement) and histologic grade.RESULTSFifteen cases were examined, with a median follow‐up of 108 months and a median age of 24 years. The median duration of symptoms was 4 weeks, and the median tumor size was 20 mm. Two patients had ductal carcinoma in situ (DCIS) only, while the other 13 patients had invasive carcinomas, none of which were Grade I. A mastectomy was performed on 8 out of 15 patients (53%). Axillary nodal metastases were present in 4 out of 12 patients (33%). Of the 13 cases of invasive disease, 9 out of 13 patients (69%) experienced recurrence and died of breast carcinoma. Median disease free survival for patients with invasive disease was 86 months. There was no difference in overall survival between the patients aged ≤ 25 years and those aged 26–35, but taken together young women ≤ 35 had a worse prognosis than women between 36 and 65, due to a higher incidence of high grade and estrogen receptor negative tumors.CONCLUSIONSThe current study suggests that among young women with breast carcinoma there is no difference in prognosis between the very young and the young. Despite two thirds of patients being node negative, the high mortality rate indicates a need for an optimal selection of adjuvant therapy among these cases. Cancer 2002;94:606–14. © 2002 American Cancer Society.DOI 10.1002/cncr.10273

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“…6 -9 Multivariate analyses to assess associations of age and menopausal status with other clinical and pathologic characteristics have not consistently retained either variable as an independent adverse prognosticator, 8 although several multivariate analyses have indicated that young age or premenopausal status are independent predictors of disease recurrence. 10 -13 In addition, a few studies have found that those women at the extremes of age, i.e., premenopausal women younger than 33 years of age 11 or postmenopausal women older than 80 -85 years of age, 3,14 had a worse prognosis than other age groups.…”

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“…The proportion of PR-positive breast carcinomas has been variably reported to be higher in older age groups, 8,[11][12][13]46 lower in postmenopausal women 54 or not varying with age or menopausal status. 16,17 Several studies have found that p27 Kip1 expression does not differ significantly by age or menopausal status.…”

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Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

Talley

Grizzle

Waterbor

et al. 2001

Intl Journal of Cancer

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Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile (including negative steroid hormone receptors and a high rate of cellular proliferation) and poor outcome than breast cancers in postmenopausal women. It has been hypothesized that this adverse prognostic profile is a result of the higher histologic grade of breast cancers in pre-compared with post-menopausal women. To assess the association of expression of steroid hormone receptors and indicators of proliferation while controlling for histologic grade, we identified 100 infiltrating ductal carcinomas from premenopausal women 45 years of age or younger and 100 from postmenopausal women 65 years of age or older. The carcinomas were selected so that the histologic grades (low versus high) were distributed equally between the 2 groups. Estrogen receptors (ER), progesterone receptors (PR), p27 Kip1 and Ki-67 (to measure rate of proliferation) were assessed by immunohistochemistry and compared between groups. Clinical information and survival data were also analyzed. ER content was lower and proliferation was higher in carcinomas in premenopausal women (p ‫؍‬ 0.048 and p ‫؍‬ 0.005, respectively). By univariate analysis, p27 Kip1 and PR were not different between the groups; however, in multivariate analysis, p27 Kip1 was higher in postmenopausal women, but only in a subgroup with highly proliferative carcinomas. Overall survival was similar in the pre-and postmenopausal women. Furthermore, low p27 Kip1 and African-American ethnicity predicted a poorer overall survival in the premenopausal, but not in the postmenopausal, women in our study. After controlling for histologic grade, a lower expression of ER and a higher proliferative index were detected in breast carcinomas in premenopausal women. Therefore, some prognostic indicators, such as ER and proliferative rate, may be more closely associated with menopausal status than histologic grade. Our data also suggest that some prognostic factors are not equally effective as predictors of survival in pre-and postmenopausal women. Prognosis in women with breast cancer has been reported to differ according to age and menopausal status. Studies examining this issue have varied in design, age categorization and outcome measures. A few large population-based studies and more limited analyses 1-5 have indicated that women under the ages of 30 -40 years have a worse prognosis. Some retrospective studies have attempted to explain the less favorable outcome in younger women and have reported that breast cancers in younger women exhibit more adverse characteristics, including a high clinical stage at diagnosis, high histologic grade, lack of steroid hormone receptors and increased proliferation. 6 -9 Multivariate analyses to assess associations of age and menopausal status with other clinical and pathologic characteristics have not consistently retained either variable as an independent adverse prognosticator, 8 although several multivariate analyses have indicated that young ag...

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Age as prognostic factor in premenopausal breast carcinoma

Cited by 429 publications

References 24 publications

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

Breast carcinoma in women age 25 years or less

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

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