Osteoporosis treatment and 10 years' oestrogen receptor+ breast cancer outcome in postmenopausal women treated with aromatase inhibitors.

BACKGROUND: Risk factors for breast cancer relapse are well-known, such as large tumour size or lymph node involvement. The aim of our study was to analyse the influence of bone mineral density, fractures and bisphosphonate or vitamin D prescription on 10 years' breast cancer outcome. PATIENTS AND METHODS: This is a longitudinal and prospective cohort of 450 postmenopausal women with local oestrogen receptor (ER)+ breast cancer. For every patient, we analysed tumour characteristics, bone status at the beginning of aromatase inhibitor treatment and 10 years' cancer outcome with Cox model. RESULTS: Mean follow-up was 10.3 ± 3.0 years. Seventy nine women died, and 75 had a relapse; 30.7% had a history of fracture, 16.9% had a T-score ≤ -2.5 and 11.3% had vitamin D deficiency. Bisphosphonates were prescribed to 35.3% women for osteoporosis for a mean duration of 5 ± 1.7 years. Tumour size (hazard ratio [HR] = 1.32, P ≤ 0.01) and the number of lymph nodes involved (HR = 1.07, P = 0.03) were significantly associated with relapse. Bisphosphonate treatment was significantly associated with a decreased risk of relapse (HR = 0.51, P = 0.03). Age at cancer diagnosis (HR = 1.07, P ≤ 0.01) and vitamin D deficiency (HR = 1.85, P = 0.04) were significantly associated with an increased risk of death, whereas bisphosphonate treatment was associated with a decreased risk of death (HR = 0.46, P = 0.01). CONCLUSION: Osteoporosis treatment, including vitamin D and bisphosphonates, is associated with a 50% reduction of relapse and death in women treated with aromatase inhibitors for ER+ breast cancer.

Fracture incidence after 3 years of aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women.

[Dosimetric study of the different techniques to deal with respiratory motion for lung stereotactic radiotherapy]. / Étude dosimétrique des différentes techniques de gestion du mouvement respiratoire pour l'irradiation thoracique en conditions stéréotaxiques.

PURPOSE: To evaluate the different respiratory movement management techniques during irradiation of lung tumours. PATIENTS AND METHODS: Seven patients with one or more primary or secondary lung lesions less than 5 cm (11 tumours in total) had three computed tomographies (CT): free-breathing, deep-inspiration breath-hold using a spirometer, and 4-dimensional (4D). From these three acquisitions, five treatment plans were performed: free-breathing (reference method), deep-inspiration breath-hold, and three from the 4D CT: two breathing synchronized treatments (inspiration and expiration) and one treatment taking into account all the tumour motions (definition of the internal target volume [ITV]). Planning target volume (PTV) size and dose delivered to the lungs were compared. RESULTS: Mean PTV with the free-breathing modality was 83 ± 28 cm(3), which was significantly greater than any of the other techniques (P<0.0001). Compared to the free-breathing PTV, PTV defined with the ITV was reduced by one quarter (63 ± 31 cm(3)), and PTV with the deep-inspiration breath-hold, breathing synchronized inspiration and breathing synchronized expiration techniques were reduced by one third (50 to 54 ± 24 to 26 cm(3)). Deep-inspiration led to significantly increase the healthy lung volume compared to other methods (mean volume of 5500 ± 1500 cm(3) versus 3540 to 3920 cm(3), respectively, P<0.0001). The volume of healthy lungs receiving at least 5 and 20 Gy (V5 and V5) were significantly higher with the free-breathing method than any of the other methods (P<0.0001). The deep-inspiration breath-hold modality led to the lowest lung V5 and V20. CONCLUSION: Deep-inspiration breath-hold technique provides the most significant dosimetric advantages: small PTV and large lung volume. However, patients must be able to hold 20 seconds of apnea. Respiratory gating also reduces the PTV, but its application often requires the implantation of fiducial, which limit its use. A 4-dimensional CT allows for a personalized and reduced PTV compared to free-breathing CT.

High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy. PATIENTS AND METHODS: A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays. RESULTS: Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < -2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4] and with spine BMD (OR 1.4, 95% CI 1.1-1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < -2.5. CONCLUSION: Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures.

[Asplenia in the Hodgkin's patient]. / L'asplénisme du patient hodgkinien.

FEWER INDICATIONS AFTER SPLENECTOMY: Real therapeutic progress has been achieved over the last fifty years for patients with Hodgkin's disease known for their chronic immunodepression. Since the advent of effective chemotherapy protocols such as ABVD, and more recently intensive chemotherapy completed as needed with an autograft, splenectomy is no longer performed for therapeutic purposes but may be indicated for its contribution to diagnosis. STRATIFICATION OF RISK OF ASPLENISM: There remain however several questions concerning the infectious complications in these patients given chemotherapy and splenic radiotherapy. One of the objectives of this work was to propose a stratification of risk of asplenism as a function of treatments administered, the level of initial immunodepression, and the age of the patient.

[Cancers of unknown origin: 311 cases]. / Cancers d'origine indéterminée: à propos de 311 cas.

Carcinoma of unknown primary site has been defined as a metastatic disease without known primary site (upon clinical, radiological or endoscopic examination) at the initial therapeutic decision. The incidence of such carcinomas is between 1.6 and 15% of all adult's tumors. The goals of this retrospective and monocentric study were 1) the incidence of these carcinoma; 2) the utility to identify the primary site; 3) the efficacy of treatment in terms of survival; and 4) the prognostic factors to optimize strategic choices. Between January 1980 to December 1995, 311 cases were identified; this represents 1.6% of all cases treated in our center. Histological analyses of metastases revealed adenocarcinoma: 164 cases (92 males, 72 females; 29 well differentiated, 11 poorly differentiated and 41 undifferentiated); squamous cell carcinoma: 90 cases (78 males, 12 females); undifferentiated carcinoma: 27 cases (21 males, 6 females); neuro-endocrine tumor: 10 cases; and others: 20 cases. Median age was 61.1 years (30-94). Half of the patients had a PS between 0 and 1. The carcinoma was revealed by only one site of metastases in 35% of the cases (lymph node 72.9%, bone 35.5%, liver 19.4% and lung 16.5%). The primary carcinoma was found in only 6% of the cases. Median survival of all patients was only 9 months. Multivariate analyses by the Cox method show four positive prognostic factors: sex (female), performance status (PS < 2), histological analyses (squamous cell carcinoma), only one site of metastases.

[Compressive dyspnea and dysphagia caused by sclerous cervical cutaneous metastasis disclosing breast carcinoma]. / Dyspnée et dysphagie compressives par métastase cutanée scléreuse cervicale révélant un carcinome mammaire.

INTRODUCTION: Cutaneous metastases from breast carcinoma are infrequently the first sign of the disease. They usually appear as cutaneous thoracic nodules. We report the case of a cutaneous sclerous metastasis from breast carcinoma revealed by acute compressive dyspnea and dysphagia. CASE REPORT: A 65 years old woman was admitted for compressive acute dyspnea and dysphagia attributed to the growth of a sclerous cervical isolated metastasis. Investigations revealed rapidly growing low-differentiated primitive breast carcinoma. Chemotherapy induced good clinical response allowing a 27 months survival, in spite of a strong chemodependance. DISCUSSION: This case-report of a breast carcinoma's metastasis is notable because of its clinical revealing signs (acute compressive dyspnea and dysphagia), clinical aspect, cervical location preceding primitive cancer's clinical expression, and long term survival with treatment. The initial submaxillary location suggest the possibility of a metastasis to submaxillary salivary glands with secondary extension to the skin.

Early events of the inflammatory reaction induced in rat brain by lipopolysaccharide intracerebral injection: relative contribution of peripheral monocytes and activated microglia.

We have previously demonstrated that lipopolysaccharide (LPS) intracerebral injection induced only minimal inflammatory reaction in rat brain, apart from an increased number of 'brain macrophages' observed 24 h after LPS administration [Montero-Menei et al., Brain Res., 653 (1994) 101-111]. However, the nature of these 'brain macrophages' in the inflammatory response is still unclear. The present study focused on the early time-points (from 5 h to 24 h) after LPS injection or stab-lesion, and was aimed at the identification of the peripheral (monocytes) or parenchymal (microglia) origin of these 'brain macrophages'. OX42- and ED1-labeling did not clearly discriminate between monocytes/macrophages and reactive microglia, both cell types being immunoreactive. In other experiments, rats were made aplasic by irradiation prior to lesioning. These experiments clearly demonstrated that LPS induces an intense monocyte recruitment and, to a lesser extent, microglial activation since about 80% of the cells present 24 h after LPS injection consisted of recruited monocytes not observed in aplasic rats. Interestingly, our data show that LPS exerts a sequential dual action by first inhibiting the monocyte recruitment observed 5 h after stab lesion and then enhancing it at 15 h and 24 h after injection. A possible involvement of cytokines, chemokines and adhesion molecules in the mechanisms occurring in the early events of brain inflammatory reaction is discussed.

[Maintenance of the dose-intensity of chemotherapy combining carboplatin, cyclophosphamide, etoposide in women with ovarian cancer aged 70 and over]. / Maintien de l'intensité de dose d'une chimiothérapie associant carboplatine, cyclophosphamide et étoposide chez la femme de plus de 70 ans atteinte d'un cancer de l'ovaire.

Elderly patients are often considered as subjects at risk for bad tolerance to chemotherapy. They are therefore treated in a less aggressive way compared with younger women. In a retrospective study, we evaluated the dose-intensity of a chemotherapy for 15 patients older than 70 years of age, presenting an ovarian carcinoma. Median age was 73 years. All but one were classified in stage III-IV and only four were presented with a complete surgery or with a pathological residue < 2 cm. Six patients were considered as non operable. Performance status (PS) was in 11 cases equal to 0 or 1. The treatment associated from D1 to D4: carboplatine 75 mg/sqm/day, cyclophosphamide 250 mg/sqm/day, etoposide 50 mg/sqm/day for six cycles each over four weeks. We compared for each drug the delivered dose-intensity (DID) all along the six cycles to the forecast dose-intensity (FID). Except for the patients with a PS > or = 2, treated in first intention by a 2/3 dose, the DID/FID ratio was > 90%. It decreased between the 1st and 3rd cycles, then remained unchanged. Treatment was well tolerated by patients with a PS < 2 whose 4/11 have presented a grade III-IV hematologic toxicity. In return, despite the initial dose reduction, 3/4 patients with a PS > or = 2 had severe complications. There were no toxic deaths. Three patients only had a delay for reinduction. Three out of six non operables at first had a surgical second-look with possibility of residual masses cutting of (3 PRh). Four patients were alive in first CR at 18, 22, 23 and 28 months. Women older than 70 years with a good performance status presenting an ovarian carcinoma can be treated as younger women are. A chemotherapy using efficient drugs can be delivered with an acceptable toxicity and a high dose-intensity.