Implications of axillary sentinel lymph node biopsy in immediate autologous breast reconstruction

For patients with invasive breast cancer, if the results of an axillary sentinel node biopsy are determined to be positive after permanent pathologic examination, the current recommendation is to perform a complete axillary node dissection. Subsequent axillary surgery may compromise the blood supply to an immediate autologous breast reconstruction. The purpose of this study was to determine which clinicopathologic factors in clinically node-negative breast cancer patients may be associated with an increased risk of positive axillary nodes. Identification of these factors will allow surgeons to modify their approach to immediate autologous breast reconstruction in these high-risk patients. The relationship between presenting clinicopathologic characteristics and the incidence of axillary metastases was analyzed by chi-square test and multivariate analysis in 167 patients with invasive breast cancer and a clinically negative axilla who underwent modified radical mastectomy with an immediate free transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction. Axillary nodal metastases were found in 35 percent of clinically node-negative breast cancer patients. Multivariate analysis showed that patient age of 50 years or younger (p = 0.019), T2 tumor stage or greater (p = 0.031), and presence of lymphovascular invasion on the initial biopsy specimen (p < 0.001) were independent predictors of axillary metastases in clinically node-negative patients. Based on these results, the authors propose an algorithm for decision making in clinically node-negative breast cancer patients who desire autologous breast reconstruction and sentinel lymph node biopsy. Options for immediate autologous breast reconstruction in patients undergoing mastectomy and axillary sentinel lymph node biopsy that may minimize the risk of vascular damage on reoperation include the use of the internal mammary artery and vein as recipient vessels for a free TRAM flap or a pedicled TRAM flap. If an axillary-based blood supply is used, the authors are considering the use of cadaveric dermis to isolate the pedicle of the flap away from the remaining axillary contents. New developments in breast cancer diagnosis and treatment necessitate a team approach, with increased communication between the breast surgeon and the plastic surgeon in planning surgery for these patients.     

Aggressiveness of breast cancers found with and without screening.

OBJECTIVE--To examine how breast cancers found by mammographic screening differ from those found outside screening. DESIGN--Comparative cohort study. SETTING--Turku, southwestern Finland. PATIENTS--126 women aged 40-74 years with breast cancer detected during the first round of mammographic screening in 1987-90 and 125 women within the same age range with breast cancer detected outside screening during the same period. MAIN OUTCOME MEASURES--Primary tumour size, axillary nodal status, histological features, oestrogen and progesterone receptor concentrations, ploidy, and S phase fraction. RESULTS--Compared with the controls women with cancers detected by screening had a smaller primary tumour (57 (46%) screened v 11 (10%) controls had tumours less than or equal to 11 mm in diameter, p less than 0.0001), and less often had axillary nodal metastases (104 (83%) screened v 71 (57%) controls node negative, p less than 0.0001). After adjustment for the smaller size of the primary tumour compared with control cancers, those cancers detected by screening were less likely to have axillary nodal metastases (odds ratio 0.44, 95% confidence interval 0.23 to 0.84), poor histological differentiation (0.20, 0.08 to 0.49), high mitotic counts (0.38, 0.15 to 0.97), tumour necrosis (0.45, 0.22 to 0.93) or to be of the ductal histological type (0.46, 0.22 to 0.95). They had low oestrogen receptor (0.29, 0.12 to 0.70) and progesterone receptor (0.35, 0.17 to 0.92) concentrations less often and had smaller S phase fractions (0.72, 0.55 to 0.96) than control cancers. CONCLUSIONS--Even after adjustment for the smaller size of screen detected breast cancers, their histological and cytometric features suggest low malignant potential. They may also be less likely to metastasise to axillary lymph nodes than cancers found outside screening.     

Oestrogen receptors and survival in early breast cancer.

Oestrogen receptor status was related to survival in 414 patients with primary breast cancer. Women with oestrogen receptors in their tumours survived significantly longer than those without receptors; this was true for both premenopausal and postmenopausal women and also when the patients were subdivided into those with and without axillary metastases. Patients with axillary metastases and no oestrogen receptors in their tumours had the worst prognosis, while women with axillary metastases and oestrogen receptors had a death rate similar to that of women with no axillary metastases and no receptors. Patients without oestrogen receptors and with no axillary metastases were identified as a high-risk group, and it would seem appropriate to include such patients in future trials for adjuvant therapy in early breast cancer.     

Early diagnosis of breast cancer: experience in a consultant breast clinic.

Of 2839 women referred to a consultant breast clinic for clinical, mammographic and thermographic examination, 480 underwent biopsy and 126 were found to have cancer. Ten percent of the tumours were occult and were classified as very early biologic disease; they were identified by routine mammography in women whose breasts were clinically normal. Biopsy of solid mass lesions non-suspicious on mammography identified 20% of the cancers; half these lesions, classified as early biologic disease, were discovered by doctors at routine annual clinical breast examination, though the earliest cancers were detected by women who were confident and competent in monthly self-examination of the breasts. Biopsy of solid mass lesions suspicious on mammography identified 70% of the cancers; these were classified as late biologic disease. Skin or nipple dimpling or retraction was evident in two thirds of the patients; their lesions seemed to be later biologically than the lesions of the patients without clinical signs, and 75% had discovered the lesions themselves accidentally.     

The role of contrast enchanced axillary ultrasonography in early breast cancer patients

The most important prognostic factor for the patients with breast cancer are metastases to axillary lymph nodes (ALNs). Preoperative ultrasound (US) combined with fine needle aspiration biopsy (US-FNAB) has been proved to be the most reliable method to detect nonpalpable axillary metastases in patients with breast cancer. Our study was aimed to examine the value of US contrast agent (CA) SonoVue in the US examination of the axilla for the detection of axillary lymph node (ALN) metastases in breast cancer patients. Therefore, two studies were performed. The first study included 27/70 patients with breast cancer who had an indeterminate result of the standard US examination of the axilla (L/T < 1.2 or MCT > 3 mm or predominantly non-hilar vessel signal) and underwent US examination with CA. In the second study, 26 breast cancer patients underwent standard axillary US examination performed independently by two skilled operators. The patients with indeterminate or malignant ALN underwent US- guided fine needle aspiration biopsy (US-FNAB). For macrometastases, the sensitivity, specificity, NPV and PPV of US-FNAB were 91%, 93%, 100% and 100%, respectively. The reproducibility of the standard US examination (the second study) was 85% (22/26 patients), and for the metastases larger than 5 mm, it was 100%. Moreover, our second study proved that the same results as with CA can be achieved by two skilled operators performing a standard US examination. The sensitivity of both operators was 92%. In the case of metastases larger than 5 mm, the reproducibility was 100%. Micrometastases remain a problem also in the hands of very experienced operators even if using CA.     

Breast cancer found at the time of breast reduction.

In a recent study involving 27,500 women who had breast reduction surgery in Ontario, Canada, 17 women who were diagnosed as having breast cancer at the time of their breast reduction surgery were identified. The aims of this study were to (1) describe a population-based series of patients who had breast cancer diagnosed at the time of breast reduction, (2) describe the treatment of these cancers, and (3) compare their survival rate with survival in patients in the general population who had breast cancer. Information about these women, their treatment, and outcome was extracted from hospital records, pathology reports, and reports from regional cancer centers. The chance of finding an invasive breast cancer at the time of breast reduction was 0.06 percent, which is lower than what has been reported previously. Sixty-seven percent of these women were treated with total mastectomy. In the remaining 33 percent, who were treated with partial mastectomy, the entire tumor was removed at the time of breast reduction. Fifty percent of the women were treated with radiation, and 25 percent were treated with chemotherapy or hormonal therapy. Compared with women in the general population of Ontario who have breast cancer, women whose breast cancer is discovered during breast reduction surgery are more likely to be treated with complete mastectomy and less likely to be treated with radiotherapy or chemotherapy. Seventy-one percent of the breast reduction group were axillary node-negative at diagnosis, compared with 58 percent in the general population of women with breast cancer. Survival from breast cancer in women diagnosed at the time of breast reduction (88 percent, 5-year survival) was better than survival from breast cancer in the general population (77 percent). These findings suggest that cancers found in women at the time of breast reduction are less advanced, possibly because they are diagnosed at an earlier stage.     

Parathyroid hormone related protein and hypercalcaemia in breast cancer.

OBJECTIVE--To see whether parathyroid hormone related protein has a humoral role in breast cancer. DESIGN--Plasma concentrations and tumour expression of parathyroid hormone related protein were determined (by two site immunoradiometric assay and immunohistochemistry respectively) in women with breast cancer and related to the presence of bone metastases and serum calcium concentrations. SUBJECTS--Plasma concentrations of parathyroid hormone related protein were measured in 57 women with early breast cancer without apparent bone metastases, 28 women with bone metastases, and 13 women with bone metastases and hypercalcaemia. Tissue positivity for parathyroid hormone related protein was determined retrospectively in 106 primary breast tumours from women without apparent bone metastases and 72 tumours from women with bone metastases, 25 of whom subsequently developed hypercalcaemia. RESULTS--Plasma parathyroid hormone related protein concentrations were detectable (greater than 0.23 pmol/l) in 12 (92%) of the 13 hypercalcaemic patients with bone metastases compared with 10 (36%) of the 28 normocalcaemic patients with bone metastases and five (9%) of the 57 normocalcaemic patients without bone metastases. Parathyroid hormone related protein concentrations were significantly higher in hypercalcaemic than normocalcaemic patients with bone metastases. Tumour staining was positive for parathyroid hormone related protein in 22 (88%) of the 25 primary breast cancers from patients with bone metastases. Tumour staining was positive for parathyroid hormone related protein in 22 (88%) of the 25 primary breast cancers from patients with bone metastases who later developed hypercalcaemia compared with 25 (53%) of the 47 from women in this group who remained normocalcaemic and 55 (52%) of the 106 early breast cancers from women without known metastases. CONCLUSION--Tumour derived parathyroid hormone related protein may have an important humoral role in hypercalcaemia associated with metastatic breast cancer.     

A follow-up study of 105 women with breast cancer following reduction mammaplasty.

Reduction mammaplasty is one of the most common procedures performed by plastic surgeons in Canada. In a recent study of 27,500 women in the province of Ontario who underwent breast reduction surgery, 105 women were identified who developed breast cancer after reduction mammaplasty. The purpose of this study was to compare women who had breast cancer and had a previous breast reduction with women who had breast cancer but did not have a breast reduction. Specifically, we wanted to document patient demographics, cancer type, surgical and nonsurgical treatment, and eventual outcome. A comparison group of non-breast reduction women was taken from the cohort of breast cancer patients in the province of Ontario, and the two groups were matched for age, year of diagnosis, and place of diagnosis. It was found that (1) the average age at diagnosis of breast cancer is significantly younger for women who have had previous breast reduction surgery than for those who have not; (2) the median interval between breast reduction and cancer is 5 years; (3) the type, location, and side of breast cancers are similar in the two groups of women; (4) breast reduction does not significantly increase or decrease survival rate from breast cancer; and (5) women who have had breast reduction receive the same treatment for their breast cancer as women who have not had reduction mammaplasty.     

The reliability and accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer

OBJECTIVE: Sentinel lymph node (SLN) biopsy is a new component of the surgical treatment of breast cancer that accurately predicts axillary status. In this study the authors evaluated the accuracy of intraoperative imprint cytology (IC) in comparison with definitive histologic evaluation of SLN in breast cancer patients. METHODS: A total 413 women with breast carcinoma and clinically negative axillary nodes underwent breast surgery and SLN biopsy. Mapping of SLN involved injection of (99m)Technecium labelled human albumin nanocolloid particles and Patent Blue dye. At the Department of Pathology, SLNs were bisected along its major axis. Both halves were imprinted 2-4 times on the slides and immediate staining with Hemacolor (Merck Germany) was performed for intraoperative examination. Imprint node negative women underwent no further surgery, while node positive women proceeded to full axillary clearance. Histological analysis of the SLN involved serial sectioning of the whole node with H&E and immunostaining for cytokeratin. RESULTS: Definitive histology revealed metastases (pN+) in 159/413 patients (38.5%): 69 (16.7%) macro metastases, 57 (13.8%) micro metastases, and 33 (8%) women with only isolated IHC positive cells or positive cell groups smaller than 0.2 mm (pNO sn+). The other 254 women had negative SLN biopsy. Imprint cytology detected 54/69 macro metastases, and 4/57 micro metastases. In the group with negative SLN (254), 2 cases were 'false positives'. CONCLUSIONS: Imprint of SLN biopsy can identify a negative axilla with high accuracy (specificity 99.2%). Overall sensitivity is only 36.5%, but macrometastases are detected in 77% which is important for performing ALDN in one session with operation of primary tumour.     

Detection of Cervical Cancer—A Study of Motivation for Cytological Screening

Annual cytological examination of cervical scrapings should virtually eliminate deaths from cervical cancer, but many deaths still occur because not all women are sufficiently motivated to have the examination.As part of a San Diego County Medical Society cancer control project, 2000 women were interviewed to evaluate motivating influences. It was found that most of the 70 per cent who had had the examination were motivated by the advice of physicians, rather than directly by lay publicity. Women who had not had the examination, more commonly the old and the poor, were not antagonistic but mostly unmotivated. Lay education to induce women to seek medical advice, and education of physicians to get them to urge and to carry out their part in routine annual cytologic examination of cervical exudate probably could bring about virtual elimination of death from cervical cancer.     

Diagnosing breast carcinoma in young women.

OBJECTIVE--To assess the individual and combined diagnostic accuracy of clinical examination, mammography, and fine needle aspiration biopsy in young women with breast cancer. DESIGN--Analysis based on case notes of patients presenting with breast cancer during 1971-89. SETTING--A combined breast clinic. PATIENTS--Consecutive series of 81 women aged less than 36 with histologically proved breast cancer presenting with a discrete mass over 19 years. MAIN OUTCOME MEASURES--Results of clinical examination, xeromammography or conventional mammography, fine needle aspiration biopsy, and examination of tissue removed by surgery. RESULTS--The clinical diagnosis was correct in 47 women and radiography in 35. Fine needle aspiration biopsy was correct in 47 of the 63 women in whom it was successfully performed. Fine needle aspiration was significantly more accurate than mammography (78% v 45%, p less than 0.01). Ten (16%) patients had negative results on clinical examination, mammography, and fine needle aspiration. CONCLUSION--Mammography alone seems inadequately sensitive to detect breast cancer in young patients. When all investigations give negative results excision biopsy is the only way of obtaining a definitive diagnosis.     

Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer

About 5% of breast cancer patients have inherited their disease because of a mutation in genes encoding either the BRCA-1 or BRCA-2 proteins. Inheriting one of these mutations confers a 50% to 87% risk of breast cancer. Many physicians faced with such a patient would, at a minimum, suggest increased and earlier screening for breast cancer by routine mammography.[1] Normally, regular mammographic screening combined with appropriate and prompt treatment can reduce mortality from breast cancer by 30% in women aged 50-59 years and by about 14%-18% in women aged 40-49. There are no controlled clinical trials for screening young women who have multiple first-degree relatives developing breast cancer before age 45, or those known to carry BRCA-1 or BRCA-2 mutations. In fact, recent advances point out that BRCA-1 and BRCA-2 gene products are needed to repair radiation damage to DNA.[4,5] Based on this finding, I propose that women with defective BRCA genes are likely to have an inordinate sensitivity to radiation, and this raises a question about the advisability of routinely screening these women by frequent mammography.     

Age as a factor in breast cancer knowledge,attitudes and screening behaviour.

OBJECTIVE: To determine whether there are age-related differences in knowledge, attitudes and behaviour with respect to breast cancer and whether the differences reflect the age-specific Canadian recommendations on breast cancer screening. DESIGN: Telephone survey. SETTING: Two cities and five towns and their surrounding areas in Alberta. PARTICIPANTS: The age-specific, randomly selected sample comprised 1284 women aged 40 to 75 years who did not have breast cancer. Of the 1741 eligible women who were contacted, 1350 (78%) agreed to participate; 66 were excluded because of age ineligibility or a history of breast cancer. MAIN OUTCOME MEASURE: Frequency of knowledge, attitudes and behaviour with respect to breast cancer, by age group. RESULTS: Knowledge of breast cancer risk factors was generally low and decreased with age. Few women were aware of the Canadian recommendations on breast self-examination, physical examination of the breasts by a health care practitioner and mammographic screening. Older women believed they were less susceptible to breast cancer than younger women and were less likely to have positive attitudes toward screening. Self-examination was performed 9 to 15 times per year by 424 women (33%), and 810 (63%) had been examined by a health care professional in the past year. Although 664 (52%) had undergone mammography, the proportion decreased with age after age 59. The main barriers to mammography were lack of physician referral and the woman''s belief that the procedure is unnecessary if she is healthy. CONCLUSIONS: Education is needed to increase breast cancer knowledge, promote the Canadian recommendations for early detection of breast cancer and decrease negative beliefs about the disease. Changes in the behaviour of women and physicians are needed to increase the use of breast self-examination, clinical breast examination by a health care professional and mammographic screening. Reaching women in the upper range (60 to 69 years) of the target group for mammographic screening should be a focus in promoting early detection of breast cancer.     

Value of the history in the office diagnosis of breast cancer.

A review of the histories of 1059 patients with breast problems seen consecutively in office consultation revealed an incidence of breast cancer of 13%. Patients over 50 years of age or whose mother or sister had had breast cancer had a substantially greater likelihood of having breast cancer. The finding of the problem on routine examination, a family history of breast cancer in a relative other than the mother or a sister, or prominent breast pain or nipple discharge made the diagnosis of cancer less likely. Menstrual status, a history of previous benign disease, nulliparity, current hormone therapy and duration of symptoms did not help identify the patient likely to have breast cancer. Much time could be saved for both doctor and patient in taking the history from patients with breast disorders. Only the patient''s age and the history of the mother and sisters with regard to breast cancer will help identify the "high-risk" patient. Other historical findings are either valueless or should be used to reassure these usually anxious women.     

A cohort study of breast cancer risk in breast reduction patients.

Surgical reduction of the female breast (reduction mammaplasty) is very common in plastic surgery. The purpose of this study was to determine whether women who have undergone breast reduction surgery are at the same, greater, or lesser risk of developing breast cancer than women who have not undergone breast reduction surgery. This study incorporates a population-based, non-concurrent cohort linkage methodology. The Canadian Institute for Health Information hospital records were used to identify all Ontario women who had undergone breast reduction surgery in Ontario between 1979 and 1992. Three computerized probabilistic record linkages were performed. The first linkage was between a file of the 28,042 Ontario women who had undergone bilateral breast reduction surgery between April 1, 1979, and December 31, 1992, and a file of incident cancer cases among Ontario women for the calendar period 1979 to 1993. Follow-up of the cohort was undertaken starting from the date of breast reduction surgery, and vital status was ascertained as of December 31, 1993, by record linkage with the Ontario Mortality Database maintained at the Ontario Cancer Registry. The incidence of cancer in the Ontario breast reduction cohort was compared with the cancer incidence of the general Ontario population after appropriate adjustments for age and calendar time period. The expected number of cancers was calculated using the "PERSON YEARS" computer program. Within the cohort, followed for an average of 6.5 years after bilateral breast reduction surgery, 101 breast cancers were observed and 165.8 were expected, for a standardized incidence ratio of 0.61 (0.50 to 0.74, 95 percent confidence interval). This effect was independent of patient age at breast reduction. This study demonstrates that there is no increased risk of breast cancer after bilateral breast reduction surgery and, in fact, a significant decreased risk existed in women followed for an average of 6.5 years.     

Screening for cancer.

Screening has proved effective for only two cancer sites, the breast and the cervix uteri. Only for these, therefore, should screening be a part of routine clinical practice. The degree to which screening is effective depends on whether appropriate groups are screened. For cancer of the breast, current evidence justifies mammographic screening every two years only from the age of 50, continuing at least to the age of 70. The place of breast self-examination and physical examination of the breasts is under investigation, but these procedures should probably be used in all women after the age of 40. For cancer of the cervix, nearly maximal efficacy is obtained by screening sexually active women every three years from the age of 25 to 60. Older women who have not been screened regularly should be screened. Other screening techniques to detect cancers, such as the rectal examination, sigmoidoscopy, and fecal occult blood tests for colorectal cancer, are still experimental. Organizational and other difficulties will prevent screening programs from making a major contribution to reducing overall cancer mortality by the year 2000. If organizational problems can be overcome, however, screening may control invasive cancer of the cervix and make a major contribution in reducing breast cancer mortality in the future.     

Self examination of the breast: is it beneficial? Meta-analysis of studies investigating breast self examination and extent of disease in patients with breast cancer.

The question whether the aggregated published research suggests that breast self examination is beneficial was explored in a meta-analysis of 12 studies including a total of 8118 patients with breast cancer that related the practice of breast self examination to regional lymph node state or tumour diameter. Based on the six studies for which data were available, 39% of patients (1115/2852) who reported having done breast self examination at least once before their illness had evidence of cancer in the lymph nodes compared with 50% of women (1348/2713) who had not done the examination. Logistic regression analysis showed this difference to be significant (odds ratio 0.66, confidence interval 0.59 to 0.74). Combining six studies which reported the circumstances of detection disclosed that 42% of women (272/652) who found their tumour while doing breast self examination had evidence of cancer in the nodes compared with 46% of women (871/1901) who found the tumour accidentally; this difference was not significant. Analysis of eight studies which used the diameter of the tumour to indicate the extent of disease tended to confirm the findings on lymph node state, in particular the benefit of premorbid breast self examination. Significantly fewer women who had practised the examination before the illness (56%; 1205/2137) had tumours of 2 cm or more diameter compared with women who had not practised the examination (66%; 1500/2260). The combined odds ratio for that analysis was 0.56, confidence interval 0.38 to 0.81. These findings appear to be good evidence of the benefit of encouraging women to practise self examination of the breasts regularly.     

Bone mineral density in patients with breast cancer in the perimenopausal period

Dual-energy X-ray absorptiometry was used to examine 54 patients with breast cancer. A clinical comparison group comprised 50 healthy women. All the examinees were aged 45 to 55 years. Bone mineral density was measured in the lumbar spine, proximal femur, and ultradistal antibrachium. The X-ray densitometric values of bone tissues in perimenopausal women with breast cancer were not found to be abnormal, which led to the conclusion that there were no significant bone metabolic disturbances. Along with this it was established that the women at this age had considerably reduced bone mineral density in the epimetaphyseal (ultradistal) forearm with evolving osteopenia. In this connection, it is expedient to identify an ultradistal portion of the antibrachium as an object of X-ray densitometric examination for the early diagnosis of impaired bone mineralization in women in the 45-to-55-year-old age group.     

Incidence of bone metastases in breast cancer patients in the United Kingdom: Results of a multi-database linkage study using the general practice research database

BackgroundBone is a frequent site for metastases among women with breast cancer. We conducted a study using the General Practice Research Database (GPRD), with linkage to the National Cancer Registry (NCR) and Hospital Episode Statistics (HES), to estimate the incidence of bone metastases in women with breast cancer in the United Kingdom.MethodsWe identified all women in the GPRD aged 20–99 with a first-time diagnosis of breast cancer between 2000 and 2006. To address potential underreporting, we developed and validated an algorithm to serve as a proxy for bone metastases. Bone metastases were defined as (1) a bone cancer diagnosis code on the same day or following breast cancer diagnosis date, or (2) another metastasis code plus codes consistent with bone metastases diagnosis or treatment using the algorithm. We sent questionnaires to a sample of general practitioners to validate these definitions.ResultsWe included 13,207 breast cancer patients (median age at diagnosis of 61 years) who contributed 70,885 person-years of follow-up. The majority of patients had stage 1 or 2 breast cancer (90.4%), and 2.6% had metastatic breast cancer at diagnosis. We identified 788 women (6.0%) with bone metastases after a median follow-up of 5.4 years. Questionnaire results validated the diagnosis of bone metastases in 88% of patients with a bone cancer code and for 70% identified with the algorithm.ConclusionThis is the first time the GPRD has been linked to HES and NCR to study the epidemiology of bone metastases, adding important information on the burden of bone metastasis.