Assisted reproductive technology treatment and risk of breast cancer: a population-based cohort study.

STUDY QUESTION: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? SUMMARY ANSWER: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. WHAT IS KNOWN ALREADY: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. STUDY DESIGN, SIZE, DURATION: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08). LIMITATIONS, REASONS FOR CAUTION: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. WIDER IMPLICATIONS OF THE FINDINGS: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Multicentre study of the risk of invasive cancer and use of sentinel node biopsy in women with a preoperative diagnosis of ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) in the breast that is diagnosed by biopsy implies a risk of upstaging to invasive carcinoma (IC) on final pathology. These patients require a sentinel lymph node biopsy (SLNB) for axillary staging. A two-stage procedure is not always feasible and precise selection of patients who should be offered SLNB is crucial. The aims were: to determine the rate of upstaging, and use of redundant and required SLNB in women with a preoperative diagnosis of DCIS; and to identify patient and tumour characteristics that increase the risk of upstaging. METHODS: Patients with DCIS treated between 2008 and 2016 were identified using Orbit operation planning system software, and those suitable for the study were selected based on review of the medical records. Upstaging rates and proportions of redundant and required SLNBs were calculated. Associations between clinicopathological characteristics and upstaging were analysed using univariable and multivariable logistic regression analyses. RESULTS: Of 1368 patients initially identified, 975 women with a preoperative diagnosis of DCIS were included in the study. Tumours in 246 of these patients (25·2 per cent) were upstaged to IC. Redundant SLNB was performed in 392 of 975 women (40·2 per cent). Forty-four patients (4·5 per cent) with a final diagnosis of IC were not offered SLNB and thus potentially undertreated. In adjusted analysis, DCIS size, palpability and mass formation identified by breast imaging were associated with increased risk of upstaging. The Van Nuys classification was not associated with upstaging. CONCLUSION: Most patients with IC on final pathology underwent SLNB, but a considerable number of patients with DCIS had a redundant SLNB. Lesion size, palpability and mass formation, but not Van Nuys classification group, are suggested risk factors for upstaging.

ANTECEDENTES: El carcinoma ductal in situ (ductal carcinoma in situ, DCIS) de mama que se diagnostica mediante biopsia implica un riesgo de infraestadiaje de un carcinoma invasivo (invasive carcinoma, IC) en la anatomía patológica final. Estas pacientes requieren una biopsia del ganglio linfático centinela (sentinel lymph node biopsy, SLNB) para la estadificación axilar. Dado que un procedimiento en dos etapas no siempre es factible, la selección precisa de pacientes a las que se debe ofrecer SLNB es crucial. El objetivo del estudio era determinar la tasa de infraestadiaje inicial y el uso repetido/requerido de SLNB en mujeres con un diagnóstico preoperatorio de CDIS. Además, se identificarán las características del paciente y del tumor que aumentan el riesgo de necesidad de re-estadificación. MÉTODOS: Un total de 1.368 mujeres con DCIS tratadas entre 2008-2016 fueron identificadas utilizando el programa informático de la planificación de las intervenciones hospitalarias. Después de la revisión de los registros médicos, se incluyeron 975 pacientes en la cohorte del estudio. Se calcularon las tasas de infraestadiaje y la proporción del uso repetido/requerido de SLNB. Las asociaciones entre las características clinicopatológicas y la necesidad de re-estadificación se analizaron mediante análisis de regresión logística univariable y multivariable. RESULTADOS: De 975 pacientes diagnosticados inicialmente de DCIS, 246 (25,2%) fueron re-estadiados a IC. Se realizó SLNB repetidas en 392 (40,2%) de estos pacientes. En 44 pacientes (4,5%) con un diagnóstico final de IC no se les ofreció la SLNB y, por lo tanto, pudieron estar potencialmente infratratados. En el análisis ajustado, el tamaño del DCIS, la palpabilidad y la presencia de una masa en las imágenes radiológicas de la mama se asociaron con un mayor riesgo de necesidad de re-estadificación por infraestadiaje inicial. La clasificación de Van Nuys no se asoció con la re-estadificación. CONCLUSIÓN: La mayoría de pacientes con IC en la patología final se sometieron a SLNB, sin embargo, un número considerable de pacientes con DCIS se sometieron a SLNB repetidas. El tamaño de la lesión, la palpabilidad y la presencia de masa, aunque no el grupo de clasificación de Van Nuys, se consideran factores de riesgo relacionados con infraestadiaje inicial y necesidad de re-estadificación final.

Pattern of mortality after menopausal hormone therapy: long-term follow up in a population-based cohort.

OBJECTIVE: To investigate long-term pattern of mortality in menopausal women according to different modalities of hormone therapy. DESIGN: Population-based prospective cohort study. SETTING: Denmark 1993-2013. POPULATION: A total of 29 243 women aged 50-64 years at entry into the Diet, Cancer and Health Cohort, enrolled 1993-97 and followed through 31 December 2013. METHODS: Cox' proportional hazards models for increasingly longer periods of follow-up time were used to estimate mortality pattern according to baseline hormone use adjusted for relevant potential confounders. MAIN OUTCOME(S): All-cause and cause-specific mortality. Outcome information was obtained from the Danish Register of Causes of Death (linkage 99.6%). RESULTS: A total of 4098 women died during a median follow up of 17.6 years. After adjustment for relevant lifestyle risk factors, hormone use had no impact on all-cause mortality, regardless of modality. Among baseline users, lower cardiovascluar disease mortality was only evident after 5 years [hazard ratio (HR) 0.54; 95% CI 0.32-0.92], but dissipated with additional follow up. Conversely, lower colorectal cancer mortality (HR 0.64; 95% CI 0.46-0.89) and higher breast cancer mortality (HR 1.34; 95% CI 1.05-1.72) only became evident after 15 years of follow up. There were no significant associations for mortality from other types of cancer or from stroke. CONCLUSIONS: In this long-term follow-up study, taking hormones during menopause was not associated with overall mortality among middle-aged women. Investigating cause-specific mortality revealed significant, albeit weak, differential associations according to both causes of death and over time, underlining the importance of carefully considering individual risks and duration of treatment when making decisions on hormone therapy. TWEETABLE ABSTRACT: Long-term follow-up study confirms no association between menopausal hormone therapy and overall mortality.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected breast cancers.

BACKGROUND: Symptomatic breast cancers may be more aggressive as compared to screen-detected breast cancers. This could favor axillary lymph node dissection (ALND) in patients with symptomatic breast cancer and positive sentinel nodes. METHOD: We identified 955 patients registered in the Danish Breast Cancer Cooperative Group (DBCG) Database in 2008 - 2010 with micrometastases (773) or isolated tumor cells (ITC) (182) in the sentinel node. Patients were cross-checked in the Danish Quality Database of Mammography Screening and 481 patients were identified as screen-detected cancers. The remaining 474 patients were considered as having symptomatic cancers. Multivariate analyses of the risk of non-sentinel node metastases were performed including known risk factors for non-sentinel node metastases as well as method of detection. RESULTS: 18% of the patients had metastases in non-sentinel nodes. This was evenly distributed between patients with symptomatic and screen-detected cancers; 18.5% vs 17.5% (OR 1.07; 95% CI 0.77-1.49; p = 0.69). In patients with micrometastases 21% had non-sentinel node metastases in the group with symptomatic cancers compared to 19% of patients with screen-detected cancers. This difference was not significant (OR 1.16; 95% CI 0.81-1.65, p = 0.43). Neither the multivariate analysis showed an increased risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected cancers (OR 1.12, CI 0.77-1.62, p = 0.55). In patients with ITCs 8% of patients with symptomatic cancers had non-sentinel node metastases compared to 13% of patients with screen-detected cancers. This difference was not significant (OR 0.58; 95% CI 0.22-1.54, p = 0.27). In the multivariate analysis, the risk of non-sentinel node metastases was still not significantly increased in patients with symptomatic cancers compared to screen-detected cancers (OR 0.45; 95% CI 0.16-1.27, p = 0.13). CONCLUSION: We did not find any clinically relevant difference in the risk of non-sentinel node metastases between patients with symptomatic and screen-detected cancers with micrometastases or ITC in the sentinel node.

Intercostobrachial nerve handling and pain after axillary lymph node dissection for breast cancer.

BACKGROUND: Moderate to severe pain in the first week after axillary lymph node dissection (ALND) for breast cancer is experienced by approximately 50% of the patients. Damage to the intercostobrachial nerve (ICBN) has been proposed as a risk factor for the development of persistent pain following breast cancer surgery but with limited information on acute post-operative pain. The aim of the present study was to examine the influence of ICBN handling on pain during the first week after ALND. METHODS: The study was part of a larger prospective cohort study on persistent pain after breast cancer treatment. Pain and sensory disturbances were assessed pre-operatively, within the first 72 h post-operatively and a week after surgery. Intraoperative handling of the nerve was recorded by the surgeon as preserved, partially preserved or sectioned. RESULTS: One hundred forty-one patients were treated with ALND level I + II, and the ICBN could be identified in 125 (89%) patients. Of the 17 not identified, eight were stated as without any sign of the nerve and were included in analysis as sectioned. Thus, the analysis included 133 patients in which 45 (34%) of these the ICBN was preserved, 39 (29%) partially preserved and 49 (37%) sectioned. At 1 week after surgery, 104 patients (78%) reported pain, whereas 35 (26%) reported moderate to severe pain. There was no difference between the ICBN groups in pain scores or sensory disturbances measured pre-operatively compared to 1 week post-operatively. CONCLUSION: The type of ICBN handling during ALND may not influence acute post-operative pain in the first week after surgery.

Multigene profiles to guide the use of neoadjuvant chemotherapy for breast cancer: a Copenhagen Breast Cancer Genomics Study.

Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) expression guide the use of neoadjuvant chemotherapy (NACT) in patients with early breast cancer. We evaluate the independent predictive value of adding a multigene profile (CIT256 and PAM50) to immunohistochemical (IHC) profile regarding pathological complete response (pCR) and conversion of positive to negative axillary lymph node status. The cohort includes 458 patients who had genomic profiling performed as standard of care. Using logistic regression, higher pCR and node conversion rates among patients with Non-luminal subtypes are shown, and importantly the predictive value is independent of IHC profile. In patients with ER-positive and HER2-negative breast cancer an odds ratio of 9.78 (95% CI 2.60;36.8), P < 0.001 is found for pCR among CIT256 Non-luminal vs. Luminal subtypes. The results suggest a role for integrated use of up-front multigene subtyping for selection of a neoadjuvant approach in ER-positive HER2-negative breast cancer.

Preoperative PET/CT in early-stage breast cancer.

BACKGROUND: The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer. PATIENTS AND METHODS: A total of 103 consecutive patients with newly diagnosed operable breast cancer with tumors ≥2 cm were independently examined preoperatively with conventional assessment (mammography, breast/axillary ultrasound, chest X-ray and blood samples) and PET/CT with no prior knowledge of the other. RESULTS: PET/CT identified a primary tumor in all but three patients (97%). PET/CT solely detected distant metastases (ovary, bones and lung) in 6 patients and new primary cancers (ovary, lung) in another two patients, as well as 12 cases of extra-axillary lymph node involvement. In 15 patients (15%), extra-axillary malignancy was detected by PET/CT only, leading to an upgrade of initial staging in 14% (14/103) and ultimately a modification of planned treatment in 8% (8/103) of patients. CONCLUSIONS: PET/CT is a valuable tool to provide information on extra-axillary lymph node involvement, distant metastases and other occult primary cancers. Preoperative (18)F-fluorodeoxyglucose-PET/CT has a substantial impact on initial staging and on clinical management in patients with early-stage breast cancer with tumors ≥2 cm.

Breast cancer incidence by estrogen receptor status in Denmark from 1996 to 2007.

During the past 50 years, breast cancer incidence has increased by 2-3 % annually. Despite many years of testing for estrogen receptors (ER), evidence is scarce on breast cancer incidence by ER status. The aim of this paper was to investigate the increase in breast cancer incidence by ER status. Data were obtained from the clinical database of the Danish Breast Cancer Cooperative Group which holds nationwide data on diagnosis, including pathology, treatment, and follow-up on primary breast cancers since 1977. All Danish women <80 years diagnosed with primary breast cancer 1996-2007 were identified in this prospective register based study. ER status was evaluated using immunohistochemical staining by standardized laboratory methods in the Danish Pathology Departments and reported to the database. From 1996 to 2007, breast cancer incidence increased overall with a tendency to level off after 2002. In all women a significant decrease was found in ER unknown tumors. However, in both pre- and postmenopausal women, significant increases were seen in incidence of ER+ tumors; though the increase levelled off for premenopausal women after 2002. In postmenopausal women, the incidence of ER- breast cancer decreased significantly throughout the period. In women <35 years, we found a minor non-significant increase in both ER+ and ER- tumors. ER unknown decreased in all women and was the most distinct in premenopausal women aged 35+. We found a significant increase in ER+ breast cancer incidence in postmenopausal women whereas the incidence in premenopausal women (aged 35+) levelled off after 2002.

Radioactive seed localisation of non-palpable lymph nodes - A feasibility study.

BACKGROUND: Radioactive seed localisation (RSL) is a preoperative localisation method using a small titanium seed containing iodine-125. The method is increasingly applied for localising non-palpable lesions in the treatment of breast cancer. We believe that RSL has the potential to be used in various surgical specialties. The aim of this feasibility study was to test RSL as a preoperative localisation of non-palpable lymph nodes. METHODS: Between November 24, 2015 and October 26, 2016, 15 patients with suspicious lymph nodes on imaging were included in the study. The lymph nodes were located in the axillary region (n = 9), the head and neck region (n = 5) and the inguinal region (n = 1). The seeds were placed in the centre of the lymph node, in the capsule or just outside the capsule guided by ultrasound. During surgery, incision and localisation of the lymph nodes were performed based on the auditory signal of the gamma probe. After excision, lymph nodes including iodine seeds were sent for pathologic examination and the seeds were returned to the Department of Nuclear Medicine. RESULTS: The non-palpable lymph nodes were all successfully marked using ultrasound. The lymph nodes were successfully localised and excised during surgery, and the procedure was performed without complications in the majority of the cases. CONCLUSION: Localisation of suspicious non-palpable lymph nodes using RSL is feasible. RSL may ease the surgical procedure, minimise trauma to the surrounding tissue and ultimately benefit the patient. Future prospective studies are necessary to determine the further use of RSL within different surgical specialties.

Variations in prognostic factors in primary breast cancer throughout the menstrual cycle.

AIMS: We investigated whether menstrual cycle dependent variations in prognostic factors are detectable in malignant breast tissue. METHODS: Since 1977 the Danish Breast Cancer Cooperative Group has collected population-based information about primary clinical data, treatment regimens and follow-up status on Danish women with breast cancer. Information about last menstrual periods prior to surgery was obtained from files recorded at the time of admission for primary surgery. Included in this study were 1060 patients self-reported to be regularly menstruating and with a menstrual period within 6 weeks of surgery and who were operated in a single-step procedure. None of the patients were current users of exogenous hormones at the time of surgery. Variations of prognostic factors throughout the menstrual cycle were evaluated. RESULTS: Overall, no significant correlation between endogenous hormone fluctuations and oestrogen receptor (ER) status and progesterone receptor (PgR) status were found. Furthermore, we observed no cycle-dependent variation for mitotic index, lymph node involvement or tumour size. CONCLUSIONS: The classical prognostic factors in breast cancer did not differ significantly throughout the menstrual cycle in the present study.

Timing of surgery in relation to menstrual cycle does not predict the prognosis in primary breast cancer. Danish Breast Cancer Cooperative Group.

From 1977 to 1989 6488 patients under 50 years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these, information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of all women operated upon during the period with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on 5 and 10 years survival.

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.

Factors influencing the effect of age on prognosis in breast cancer: population based study.

OBJECTIVE: To investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment influences such an association. DESIGN: Retrospective cohort study based on a population based database of patients with breast cancer containing detailed information on tumour characteristics, treatment regimens, and survival. SETTING: Denmark. SUBJECTS: 10 356 women with primary breast cancer who were less than 50 years old at diagnosis. MAIN OUTCOME MEASURES: Relative risk of dying within the first 10 years after diagnosis according to age at diagnosis after adjustment for known prognostic factors and expected mortality. RESULTS: Overall, young women with low risk disease who did not receive adjuvant treatment had a significantly increased risk of dying; risk increased with decreasing age at diagnosis (adjusted relative risk: 45-49 years (reference): 1; 40-44 years: 1.12 (95% confidence interval 0.89 to 1.40); 35-39 years: 1.40 (1.10 to 1.78); <35 years: 2.18 (1.64 to 2.89). However, no similar trend was seen in patients who received adjuvant cytotoxic treatment. The increased risk in younger women who did not receive adjuvant treatment compared with those who did remained when women were grouped according to presence of node negative disease and by tumour size. CONCLUSION: The negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease who did not receive adjuvant cytotoxic treatment. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic treatment.

[The significance of reproductive history for prognosis of primary breast cancer]. / Fødselsmønsterets betydning for prognosen ved primaer mammacancer.

The aetiological impact of a woman's reproductive history on breast cancer is well established, whereas the prognostic influence of the reproductive pattern is less well described. A literature search with focus on three Danish studies is described. Status as parous/nulliparous and number of births appear to have no prognostic influence. Women who have their first child at an early age have a lower survival than women who have postponed their first childbirth. This may eventually be explained by selection, i.e. that women with an early first full-term pregnancy represent a group with a more malignant disease. Women diagnosed in the first two years after childbirth have a significantly lower survival, probably because the cancer, being subclinical during pregnancy, is affected by the high oestrogen concentrations with aggressive growth as the outcome. Pregnancy after treatment of breast cancer does not appear to have a negative influence on the prognosis.

[Should all younger patients with breast cancer be offered adjuvant cytotoxic chemotherapy?]. / Bør alle yngre mammacancerpatienter tilbydes adjuverende cytotoksisk kemoterapi?

The aim of the study was to investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment may influence such an association. It was conducted as a retrospective cohort study based on a population-based data-base of breast cancer diagnosis with detailed information on tumour characteristics, treatment regimens, and vital status and included 10,356 patients with primary breast cancer less than 50 years of age at diagnosis. The main outcome measures were relative risk of dying within the first ten years after diagnosis according to age at diagnosis, adjusted for effect of known prognostic factors and expected mortality. Overall, young patients with low risk disease who did not receive adjuvant treatment had a significantly increasing risk of dying with decreasing age at diagnosis (adjusted relative risk: 45-49 years: 1 (reference); 40-44 years: 1.12 (0.89-1.40); 35-39 years: 1.40 (1.10-1.78); < 35 years: 2.18 (1.64-2.89). However, a similar trend was not seen in young patients who received adjuvant cytotoxic therapy. We found the same difference as above when comparing women receiving no treatment with those receiving adjuvant cytotoxic therapy within strata of node negative patients and patients with the same tumour size. In conclusion, the negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease not receiving adjuvant cytotoxic therapy, whereas young women who receive adjuvant cytotoxic therapy have the same prognosis as middle-aged women. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic therapy.

[Menstrual cycle and surgery of breast cancer. Point of time for the surgery of primary breast cancer in connection with menstrual cycle is without prognostic significance]. / Menstruationscyklus og operation for mammacancer. Tidspunktet for operation for primoer mammacancer i forhold til menstruationscyklus er uden prognostisk betydning.

From 1977 to 1989 6488 patients under fifty years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of the total group with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on five- and ten year survival.

Cross-validation of three predictive tools for non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node.

BACKGROUND: We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients who might benefit from further axillary treatment. MATERIAL AND METHOD: Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577 Danish patients with micrometastases and 304 Danish patients with ITC, respectively. The models were cross-validated in the opposite cohort. RESULTS: The Danish model for micrometatases was accurate when tested in the Finnish cohort, with a slight change in AUC from 0.64 to 0.63. The AUC of the Finnish model decreased from 0.68 to 0.58 when tested in the Danish cohort, and the AUC of the Danish model for ITC decreased from 0.73 to 0.52, when tested in the Finnish cohort. The Danish micrometastatic model identified 14-22% of the patients as high-risk patients with over 30% risk of non-sentinel node metastases while less than 1% was identified by the Finish model. In contrast, the Finish model predicted a much larger proportion of patients being in the low-risk group with less than 10% risk of non-sentinel node metastases. CONCLUSION: The Danish model for micrometastases worked well in predicting high risk of non-sentinel node metastases and was accurate under external validation.