The impact of changes in hormone therapy on breast cancer incidence in the US population.

OBJECTIVE: This study combines population changes in hormone therapy (HT) use with reported relative risks to estimate directly the impact of reductions in HT use on US breast cancer incidence. METHODS: Using breast cancer incidence rates and prevalence estimates of HT use, the breast cancer incidence in HT users and non-users was derived. Attributable fraction calculations used risk data from the Million Women Survey (MWS), Collins' meta-analysis (CMA), and the initial or later data from the Women's Health Initiative (WHI) study. RESULTS: Between 2000 and 2005, HT use fell from 25.0 to 11.3%. The reported breast cancer incidence (in women aged 40-79) fell 8.8%. Derived incidence rates among non-users of HT remained unchanged (MWS or later WHI data) or slightly lower (initial WHI and CMA data), suggesting reductions in incidence are almost entirely (MWS or later WHI data) or partially (initial WHI or CMA data) due to reduced HT use. CONCLUSION: Changes in reported breast cancer incidence may be partially or largely explained by changes in HT use in the US population.

Multifocal and multicentric breast cancer: does each focus matter?

PURPOSE: The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer. METHODS: The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity. RESULTS: Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas. CONCLUSION: The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.

Tumour size as a predictor of axillary node metastases in patients with breast cancer.

BACKGROUND: The ability to predict the behaviour of breast cancer from its dimensions allows the clinician to inform a woman about the absolute benefits of adjuvant therapies or further surgery to control her disease. Tumour size and grade are independent predictors of nodal disease. This study aims to generate a tool, using Australian data, allowing surgeons to calculate the probability of axillary lymph node involvement in a preoperative setting. METHODS: The histological reports of patients with breast cancer treated in 1995 in New South Wales were examined and tumour size, grade and nodal status recorded. Univariate and multivariate analyses identified predictors of node positivity and, using linear regression analysis, a simple formula to predict nodal involvement was derived. RESULTS: In a 6-month period, 754 women had non-metastatic, unifocal breast cancer treated with surgery and complete axillary dissection and 283 (37.5%) had positive nodes. Tumour size remained an independent predictor of node positivity and the probability (%), y, of nodal involvement may be predicted by the formula y = 1.5 x tumour size (mm) + 7, r = 0.939 and P = 0.001. CONCLUSIONS: This paper shows the need to assess the axilla in every patient because even patients with small tumours (0-5 mm) have the possibility of axillary involvement (7-14.5%). Use of this simple formula allows clinicians and patients to make informed decisions about the possible need for a full axillary dissection to reduce the chance of understaging and potentially undertreating a woman's breast cancer.

Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT.

OBJECTIVE: To quantify the journeys and CO2 emissions if women with breast cancer are treated with risk-adapted single-dose targeted intraoperative radiotherapy (TARGIT) rather than several weeks' course of external beam whole breast radiotherapy (EBRT) treatment. SETTING: (1) TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy, (2) 2 additional UK centres offering TARGIT. PARTICIPANTS: 485 UK patients (249 TARGIT, 236 EBRT) in the prepathology stratum of TARGIT-A trial (where randomisation occurred before lumpectomy and TARGIT was delivered simultaneously with lumpectomy) for whom geographical data were available and 22 patients treated with TARGIT after completion of the TARGIT-A trial in 2 additional UK breast centres. OUTCOME MEASURES: The shortest total journey distance, time and CO2 emissions from home to hospital to receive all the fractions of radiotherapy. METHODS: Distances, time and CO2 emissions were calculated using Google Maps and assuming a fuel efficiency of 40 mpg. The groups were compared using the Student t test with unequal variance and the non-parametric Wilcoxon rank-sum (Mann-Whitney) test. RESULTS: TARGIT patients travelled significantly fewer miles: TARGIT 21 681, mean 87.1 (SE 19.1) versus EBRT 92 591, mean 392.3 (SE 30.2); had lower CO2 emissions 24.7 kg (SE 5.4) vs 111 kg (SE 8.6) and spent less time travelling: 3 h (SE 0.53) vs 14 h (SE 0.76), all p<0.0001. Patients treated with TARGIT in 2 hospitals in semirural locations were spared much longer journeys (753 miles, 30 h, 215 kg CO2 per patient). CONCLUSIONS: The use of TARGIT intraoperative radiotherapy for eligible patients with breast cancer significantly reduces their journeys for treatment and has environmental benefits. If widely available, 5 million miles (8 000 000 km) of travel, 170 000 woman-hours and 1200 tonnes of CO2 (a forest of 100 hectares) will be saved annually in the UK. TRIAL REGISTRATION NUMBER: ISRCTN34086741; Post-results.

HRT and breast cancer: impact on population risk and incidence.

This study has calculated the potential impact of hormone replacement therapy (HRT) on breast cancer incidence in Australia and has estimated how changes in prescribing HRT to women could affect this risk. The effects of HRT on breast cancer incidence was estimated using the attributable fraction technique with prevalence data derived from the 2001 Australian Health Survey and published rates of breast cancer relative risks from HRT use. In Australia, 12% of adult women were current HRT users and in 2001, 11783 breast cancers were reported. Of these, 1066 (9%) were potentially attributable to HRT. Restricting HRT use to women aged less than 65 years, ceasing HRT prescribing after 10 years or limiting combined oestrogen and progesterone HRT to five years (but otherwise keeping prescription levels to 2001 levels) may reduce the annual breast cancer caseload by 280 (2.4%), 555 (4.7%) or 674 (5.7%), respectively. In conclusion, this study has demonstrated that when HRT prevalence is relatively high, the effect on breast cancer incidence in the population will be significant. A small modification in HRT prescribing practices may impact breast cancer incidence in Australia with associated financial and health care provision implications.

Internal mammary sentinel nodes: ignore, irradiate or operate?

INTRODUCTION: This study describes the results of internal mammary chain (IMC) biopsy, identifying factors that predict 'hot spots' and nodal metastases for patients in whom mapped IMC nodes were routinely dissected. METHODS: The nodal basin and status of every axillary and IMC site identified by lymphoscintigraphy were examined. Binary logistic regression analysed the relationship of several patients and tumour factors with IMC hot spots and metastases. RESULTS: Ninety of 490 patients (18.4%) had IMC sentinel lymph nodes (SLNs) identified by lymphatic mapping and dissected, and 20 of these (22.2%) were found to have metastases. Mapping to the IMC was most likely for women aged under 35 years (29.4%) (p=0.117), women aged 35-44 (22.6%) (p=0.034) or those with medial (23.7%) or central tumour location (22.2%) (p=0.014; p=0.062, respectively). Predictors of IMC positivity included age <35 years (p=0.063), grade 3 histology (p=0.018) and lymphatic vascular invasion (LVI) (p=0.032). Although IMC positivity was more likely with positive axillary nodes, this trend was not significant. CONCLUSION: We identified several factors (age <35 years, tumour grade and LVI) that independently predict IMC SLN identification and positivity for patients with stage I or II breast cancer. Where IMC hot spots are not dissected, we predict IMC positivity of 50% or more for young women (<35 years) or women with high grade or LVI positive tumours, and these women may benefit from more intensive chemotherapy and radiotherapy to the IMC.

Hormone replacement therapy and breast cancer risk in California.

Numerous studies have documented increased breast cancer risks with hormone replacement therapy (HRT), but these do not give a woman her specific absolute risk for the remainder of her life. This article estimates the magnitude of the effect of HRT on breast cancer incidence in California and calculates a woman's cumulative risk of breast cancer with different formulations and durations of HRT use. The effects of HRT on the underlying breast cancer incidence were estimated using the attributable fraction method, applying HRT prevalence data from the 2001 California Health Interview Survey and published rates of higher relative risk (RR) from HRT use from the Women's Health Initiative (WHI) study and Million Women's Survey (MWS). The annual number of breast cancers potentially attributable to HRT in California was estimated, along with individual cumulative risk of breast cancer for various ages to 79 years according to HRT use, duration, and formulation. Using the WHI data, 829 of 19,000 breast cancers (4.3%) in California may be attributable to HRT. This figure increases to 3401 (17.4%) when the MWS RRs are applied. Use of estrogen-only HRT or short-term (approximately 5 years) use of combined HRT has a minimal effect on the cumulative risk calculated to the age of 79 years; application of the MWS data to a Californian woman commencing HRT at the age of 50 years (no HRT, 8.5%; estrogen only, 8.6%; combined, 9.1%). Prolonged (approximately 10 years) use of combined HRT increases the cumulative risk to 10.3%. This article demonstrates that HRT will generate a small additional risk of breast cancer in an individual. The reduction in perimenopausal symptoms may be considered sufficient to warrant this extra risk. However, this view needs to be balanced because the small increases in individual risk will be magnified, producing a noticeable change in population cancer caseload where HRT use is high.