Global Disparities in Breast Cancer Genetics Testing, Counselling and Management.

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

Lymph node harvest in breast cancer patients with and without preoperative scintigraphy

Background: Sentinel lymph node biopsy (SLNB) is the standard of care for women with node negative breast cancer. Tc99 nanocolloid is a popular tracer, facilitating preoperative lymphoscintigraphy to identify sentinel nodes. This study compares the number of sentinel lymph nodes identified at the time of surgery in women who had lymphoscintigraphy with those who did not.Method: All women with primary breast cancer undergoing a SLNB from 2003­2017 who were node negative and did not have neoadjuvant chemotherapy were retrospectively reviewed in this study.Results: 576 women who had Tc99 preoperative injection were included in the study. Three hundred patients (Group 1) underwent lymphoscintigraphy preoperatively and 276 (Group 2) had no lymphoscintigraphy. The mean age at diagnosis for Groups 1 and 2 were 56 and 58 years, respectively. Both groups were also found to be similar in terms of histological subtype, tumour location, size, and HER2- and Estrogen receptor (ER) status. The surgery for the breast primary was similar in groups 1 and 2. While both groups had a median number of 2 nodes identified, the mean number of nodes identified for Group 2 (2.12) was 10% higher than for Group 1 (1.92) (p = 0.0026).Conclusion: This is the largest series to show that a preoperative lymphoscintigram (scan) can safely be omitted when performing a SLNB. As newer tracers are being used (e.g. Iron Oxide), it is important to know that accuracy of SLNB is not compromised by omission of a scan

Risk factors for lymphoedema in women with breast cancer: A large prospective cohort.

A prospective study was conducted to identify women at increased risk for lymphoedema (LE) based on axillary surgery. Assessment occurred prior to surgery, within 4 weeks, and at 6, 12 and 18 months following surgery. Following post-surgery assessment, women were asked to complete weekly diaries regarding events that occurred in the previous week. Risk factors were grouped into demographic, lifestyle, breast cancer treatment-related, arm swelling-related, and post-surgical activities. Bioimpedance spectroscopy thresholds were used to determine presence of LE. At 18-months, 241 women with <5 nodes removed and 209 women with ≥5 nodes removed were assessed. For those with <5 nodes removed, LE was present in 3.3% compared with 18.2% for those with ≥5 nodes removed. There were insufficient events to identify risk factors for those with <5 nodes removed; for those with >5 nodes removed, independent risk factors included presence of arm swelling at 12-months (Odds Ratio (OR): 13.5, 95% CI 4.8, 38.1; P < 0.01), at 6-months (5.6 (2.0, 16.9); P < 0.01), and radiotherapy to the axilla (2.6 (0.7, 8.9); P = 0.14). Arm swelling at 6 and 12 months was associated with taxane-based chemotherapy, high body weight at diagnosis and arm swelling within 4 weeks post-surgery. Of the post-surgical events assessed in a sub-group of women with >5 nodes removed and who maintained weekly diaries, only blood drawn from the 'at-risk' arm was identified as a potential risk (OR 2.0; 0.8, 5.2). For women with ≥5 nodes removed, arm swelling in the first year poses a very strong risk for presence of LE at 18-months.

A risk index for early node-negative breast cancer.

BACKGROUND: This study compared the application of the St Gallen 2001 classification with a risk index developed at the New South Wales Breast Cancer Institute (BCI Index) for women with node-negative breast cancer treated without adjuvant systemic therapy. METHODS: The BCI risk categories were constructed by identifying combinations of prognostic indicators that produced homogeneous low-, intermediate- and high-risk groups using the same variables as in the St Gallen classification. RESULTS: The BCI low-risk category consisted of women aged 35 years or more with a grade 1 oestrogen receptor (ER)-positive tumour 20 mm or less in diameter, or with a grade 2 ER-positive tumour of 15 mm or less. This category constituted 40.1 per cent of patients, with a 10-year distant relapse-free survival (DRFS) rate of 97.2 per cent. The BCI intermediate-risk category included women aged 35 years or more with a grade 2 ER-positive tumour of diameter 16-20 mm, or a grade 1 or 2 ER-negative tumour measuring 15 mm or less, and comprised 12.1 per cent of the women, with a 10-year DRFS rate of 88 per cent. The high-risk category comprised 47.7 per cent of women, with a 10-year DRFS rate of 68.4 per cent. CONCLUSION: If confirmed in other data sets, the BCI Index may be used to identify women at low risk of distant relapse (2.8 per cent at 10 years) who are unlikely to benefit from adjuvant systemic therapy, and women at intermediate risk of distant relapse (12 per cent at 10 years) in whom the benefit of adjuvant systemic therapy is small.

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

BACKGROUND: The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. METHODS: The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. RESULTS: When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. CONCLUSION: The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS: Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS: Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (> or = 1 mm). CONCLUSIONS: The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN.

Probability of axillary node involvement in patients with tubular carcinoma of the breast.

BACKGROUND: The aim of this study was to investigate the frequency of axillary metastasis in women with tubular carcinoma (TC) of the breast. METHODS: Women who underwent axillary dissection for TC in the Western Sydney area (1984--1995) were identified retrospectively through a search of computerized records. A centralized pathology review was performed and tumours were classified as pure tubular (22) or mixed tubular (nine), on the basis of the invasive component containing 90 per cent or more, or 75--90 per cent tubule formation respectively. A Medline search of the literature was undertaken to compile a collective series (20 studies with a total of 680 patients) to address the frequency of nodal involvement in TC. A quantitative meta-analysis was used to combine the results of these studies. RESULTS: The overall frequency of nodal metastasis was five of 31 (16 per cent); one of 22 pure tubular and four of nine mixed tumours (P = 0.019). None of the tumours with a diameter of 10 mm or less (n = 16) had nodal metastasis compared with five of 15 larger tumours (P = 0.018). The meta-analysis of 680 women showed an overall frequency of nodal metastasis in TC of 13.8 (95 per cent confidence interval 9.3-18.3) per cent. The frequency of nodal involvement was 6.6 (1.7--11.4) per cent in pure TC (n = 244) and 25.0 (12.5--37.6) per cent in mixed TC (n = 149). CONCLUSION: A case may be made for observing the clinically negative axilla in women with a small TC (10 mm or less in diameter).

Dual phase 99m-technetium Sestamibi imaging with single photon emission computed tomography in primary hyperparathyroidism: influence on surgery.

The purposes of this study were to determine the positive and negative predictive values of 99m Technetium (99mTc) Sestamibi dual phase imaging with single photon emission computed tomography (SPECT) for parathyroid adenomata or hyperplasia and the effect of preoperative localization on duration of surgery. We reviewed 33 adults (14 men, 19 women; mean age 53 years) with newly diagnosed primary hyperparathyroidism who underwent neck exploration. The duration of surgery for this cohort was compared with a group of historical controls (n = 53) who underwent surgery without preoperative SPECT. At surgery, there were 21 adenomata (including one carcinoma), 10 patients with hyperplasia and two with no pathology detected. The positive predictive values (PPV) for adenomata and hyperplasia were 95% and 100%, respectively. The negative predictive values (NPV) for these entities were 67% and 22%, respectively. The mean weight of adenomata detected was 3.4 g (range 0.2-17 g). Mean duration of surgery was 112.6 min as compared with 113 min in the historical controls (P = not significant). We conclude that 99mTc Sestamibi dual phase imaging with SPECT has an excellent PPV for parathyroid adenomata and hyperplasia, but does not contribute to reduced duration of surgery in patients undergoing neck exploration for the first time. The NPV is low, suggesting that a negative result does not exclude an adenoma or hyperplasia.

Complex sclerosing lesion: the lesion is complex, the management is straightforward.

BACKGROUND: Complex sclerosing lesion (CSL) and its smaller counterpart, the radial scar (RS), are frequently seen pathological entities. They are clinically asymptomatic and, prior to the implementation of mammographic screening, were most commonly found incidentally during pathological examination of other biopsied lesions. Complex sclerosing lesions are being detected regularly on mammograms due to widespread screening; many of their features resemble those of malignancy. Management varies and has been controversial. METHODS: Twenty-three cases of CSL detected during the first prevalent round of screening at BreastScreen Western Sydney (from February 1993 until June 1995) are presented and reviewed. Assessment was by a combination of radiological, clinical and cytological work-up prior to surgical biopsy. In addition, 126 spiculated carcinomas detected in the same period were reviewed and compared. RESULTS: Fourteen RS/CSL (62%) had lucent centres and nine (38%) had a central mass; three had been diagnosed provisionally as RS/CSL. Spicule lengths ranged from 25 to 90 mm; central masses ranged from 5 to 50 mm; and mass:spicule length ratio ranged from 1.2:1 to 1:10. Calcification (benign or indeterminate) was present in six cases (29%). No RS/CSL contained 'suspicious' calcifications, whereas 120 of 126 carcinomas (95%) had a central mass and six (5%) had a lucent centre (spicule lengths: 10-90 mm; central mass: 5-40 mm; and mass:spicule length ratio: 1.1:1-1:10). Twenty-one spiculated carcinomas (17%) contained microcalcifications (14 benign or indeterminate; seven suspicious). Provisional radiological diagnosis (PRD) after mammogram, with or without ultrasound, for histologically confirmed RS/CSL, was RS/CSL in 18 cases (78%), carcinoma in four cases (17%) and equivocal in one case (5%). For eight (6.5%) spiculate carcinomas the PRD was RS/CSL prior to histological diagnosis. The RS/CSL were detected with equal frequency in right and left breasts, and 22 (96%) lesions occurred in the upper breast. Seven RS/CSL (31%) and 83 spiculated carcinomas (65%) had been described as 'palpable' but most were subtle. Twelve fine-needle aspiration biopsies were performed (six 'palpable' lesions (no radiological guidance); four with ultrasound guidance and two with stereotactic guidance), and five (62.5%) of eight adequate lesions were reported as benign, two (25%) were reported as atypical, and one (12.5%) was reported as suspicious. CONCLUSIONS: Definitive mammographic and sonographic differentiation of RS/CSL and stellate-type carcinoma is impossible. For screen-detected lesions that may be RS/CSL, the appropriate surgical procedure is a small but adequate biopsy using guidewire or other localization methods with optimal cosmetic incision.

Frequency and predictors of axillary lymph node metastases in invasive breast cancer.

BACKGROUND: The objectives of the present study were to evaluate the incidence and predictors of axillary lymph node metastases (ALNM) in patients with breast cancer, and to identify if axillary surgery could be safely omitted in selected patients. METHODS: Between January 1996 and May 2000, 492 patients underwent 501 axillary lymph node dissections (ALND). The incidence of ALNM was correlated with clinical and pathological characteristics by univariate and multivariate analyses. RESULTS: Axillary lymph node metastases were found in 41% (207/501) of cases. Univariate analysis showed that palpability of primary and axillary lymph node (ALN), pathological tumour size, grade, lymphovascular invasion (LVI) and multifocality or multicentricity were significant predictors of ALNM. By multivariate analysis, palpability of ALN, pathological tumour size, LVI and multifocality or multicentricity remained as independent predictors. Among the 431 cases without palpable ALN, no ALNM were found if the tumour was < or = 5 mm, non-multifocal or multicentric, and without LVI, or the tumour was a tubular or mucinous carcinoma < or = 15 mm (n = 21). The frequency of ALNM in the absence of the other risk factors was 11% (7/64) if the tumour size was > 5-10 mm, and 17% (19/113) if the tumour was > 10-20 mm. However, the incidence of ALNM was 72% for the 32 clinically node-negative cases with multifocal or multicentric tumour > or = 10 mm and LVI. Those patients with palpable ALN (n = 66) had a greater than 50% risk of ALNM. CONCLUSIONS: Routine ALND could be omitted in clinically node-negative patients with either a < or = 5-mm, LVI-negative tumour, or a < or = 15-mm tubular or mucinous carcinoma. Axillary lymph node dissection is still useful for determining pathological nodal status in all other cases, and in most cases with palpable ALN, as a therapeutic manoeuvre.

Treatment of the axilla in early breast cancer: past, present and future.

BACKGROUND: The optimal treatment of the axilla in early breast cancer is controversial. The present study reviews the pattern and predictors of regional recurrence (RR) and prognosis after RR in patients with early breast cancer treated by conservative surgery and radiotherapy (CS + RT). Implications of the results on current practice and future directions are explored. METHODS: Between 1979 and 1994, 1158 patients with stage I or II breast cancer were treated with CS + RT at Westmead Hospital. Two groups of patients were compared: 782 patients who underwent axillary dissection (axillary surgery group) and 229 patients who received radiotherapy (axillary RT group) as the only axillary treatment. At least 10 lymph nodes were dissected in 82% of the axillary surgery group. Of the women in the RT group, 90% received RT to the axilla and supraclavicular fossa (SCF) only and 10% also received RT to the internal mammary chain (IMC). RESULTS: With a median follow-up period of 79 months for the axillary surgery group and 111 months for the axillary RT group, 27 patients developed a RR (2.8% and 2.2%, respectively). Seven patients (0.9%) in the axillary surgery group and three patients (1.3%) in the axillary RT group developed a RR in the axilla (P, not significant). Of the patients with SCF recurrences, 14 (1.8%) were in the axillary surgery group and one (0.4%) in the axillary RT group (P, not significant). One patient in the axillary surgery group developed concurrent axillary and SCF recurrences, while a patient in the axillary RT group developed an IMC recurrence. Twenty (74%) of the 27 patients with a RR developed a concurrent or subsequent distant relapse (30% and 44%, respectively). In the pathologically node-positive patients, the axillary recurrence rate was higher in those who had less than five nodes removed (17%) than those who had 10 or more nodes removed (0%; P = 0.01). The SCF recurrence rate was higher in patients with four or more positive axillary nodes (9.5%) than in those with 0-3 positive nodes (1.5%; P = 0.003). CONCLUSION: Adequate treatment of the axilla by surgery or RT alone is associated with a low rate of RR. The incidence of distant relapse was substantial in patients who developed a RR, which gives emphasis to the importance of optimizing local-regional control.

Prognosis after breast recurrence following conservative surgery and radiotherapy in patients with node-negative breast cancer.

BACKGROUND: Breast conservation surgery with radiotherapy is a safe and effective alternative to mastectomy for early-stage breast cancer. This retrospective study examined the outcome of patients with isolated local recurrence following conservative surgery and radiotherapy in node-negative breast cancer. METHODS: Between November 1979 and December 1994, 503 women with node-negative breast cancer were treated by conservation surgery and radiotherapy without adjuvant systemic therapy. RESULTS: After a median follow-up of 73 months the 5-year rate of freedom from local recurrence was 94 per cent. Thirty-five patients developed an isolated local recurrence within the breast as a first event. Thirty-three patients were treated with salvage mastectomy and two patients were treated with systemic therapy alone. The 5-year rate of freedom from second relapse was 46 per cent and the overall 5-year survival rate was 59 per cent for patients who had salvage mastectomy. Patients who developed breast recurrence as a first event had a 3.25 greater risk of developing distant metastasis (P < 0.001) than those who did not have breast recurrence as a first event. CONCLUSION: Salvage mastectomy after local recurrence was an appropriate treatment if there was no evidence of distant metastasis. Breast recurrence after conservative surgery and radiotherapy in node-negative breast cancer predicted an increased risk of distant relapse.

Conservative surgery and radiation therapy for invasive lobular carcinoma of the breast.

BACKGROUND: There is debate as to whether infiltrating lobular carcinoma (ILC) can be effectively treated with breast conservative surgery (CS) and radiotherapy (RT) because of a perceived high risk of local recurrence. This retrospective study examined the outcome of patients with ILC treated by CS and RT. METHODS: Between November 1979 and December 1994, 57 women with UICC Stage I or II ILC were treated by CS and RT at Westmead Hospital, New South Wales, Australia. The median age was 55 years (range 28-79). Twelve patients (21%) underwent a re-excision after initial CS. The final margins were clear for 43 patients (75.4%), positive (invasive or in situ) for nine patients (15.8%), and indeterminate for five patients (8.8%). All patients received whole-breast irradiation (45-50.4 Gy) usually supplemented by a boost (10-30 Gy). Fifty-three of 57 patients (93%) had their pathology reviewed at Westmead Hospital. RESULTS: After a median follow up of 69 months (range 36-162) three patients (5.3%) developed a local recurrence. One of 43 patients (2.3%) with known clear margins developed a local recurrence compared with two of 14 patients (14.3%) with positive or indeterminate margins (P = NS). The 5- and 10-year rates of freedom from local recurrence were 96 and 93%, respectively. The 5-year disease-free survival was 85% (node-negative, 92%; node-positive, 66%). Overall survival was 94% at 5 years. No patient developed a contralateral breast cancer. CONCLUSION: Patients with ILC can be effectively treated with CS and RT.

Management of high-risk node-positive breast cancer by standard-dose chemotherapy and loco-regional radiotherapy.

One-hundred, thirty-six women, aged up to 76 years, with high-risk breast cancer were treated with postoperative radiotherapy and 9 cycles of adjuvant chemotherapy in standard doses. Treatment-related toxicity was mild. At a median follow-up of 7.3 years, 39.6% are disease-free. At 5 and 10 years overall survival was 55% and 34% respectively; disease-free survival was 39% and 33% respectively. Eighteen patients (13.2%) developed loco-regional recurrence, which was uncontrolled in four. When compared to series treated with adjuvant chemotherapy, but without radiotherapy, there are apparent survival gains of 10-15% at 5 and 10 years. These results in both pre- and post-menopausal patients compare favourably with results of high-dose chemotherapy and stem-cell rescue in much more highly selected patients.

Breast carcinoma in a fibroadenoma: diagnosis by fine needle aspiration cytology.

We describe a case of ductal carcinoma in situ (DCIS) occurring in a fibroadenoma diagnosed by fine needle aspiration (FNA) cytology. The cytological features comprised a small population of pleomorphic cells admixed with a dominant population of bland epithelial cells showing features consistent with those of a fibroadenoma. Excision biopsy confirmed the presence of DCIS within an otherwise typical fibroadenoma. Recent reviews have emphasised the potential for fibroadenoma to cytologically mimic carcinoma, leading to false positive findings, however the converse is also possible. We conclude that a false negative cytological diagnosis may be avoided by recommending histological confirmation by excision biopsy when significant atypia is present, even if the overall pattern is that of a fibroadenoma.

Is there a role for fine-needle aspiration in radial scar/complex sclerosing lesions of the breast?

The fine-needle aspiration cytology (FNA) from 12 mammographically detected, histologically confirmed radial scar/complex sclerosing lesions (RS/CSL) and their corresponding mammography were reviewed. Six aspirates were obtained by palpation, four by ultrasound guidance, and two by stereotactic guidance. Of the eight lesions with sufficient material five (62.5%) were reported as benign, two (25%) as atypical, and one (12.5%) as suspicious. It is proposed that FNA for RS/CSL should not be performed, and lesions require excision for histologic assessment.

Ductal carcinoma in situ. Part 2: Treatment.

Several dilemmas exist when treating a patient with ductal carcinoma in situ (DCIS): the high rate of inter-observer variation for pathologists who must diagnose these tumours; the potential for over- and under-treatment; and the uncertainty about the best way to inform a patient who must often make a decision between breast conservation and mastectomy. Mastectomy is nearly 100% curative, is expedient, but may represent over-treatment for many women, particularly those with asymptomatic mammographically detected lesions. Axillary dissection is not recommended as a routine except for patients with lesions over 5 cm in whom the risk of micro-invasion and lymph node involvement increases. Conservative surgery (CS) alone is associated with a local recurrence rate of approximately 20%, and half of these recurrences (10% overall) are invasive, with a potential long-term cure rate of at least 90%. The addition of radiation to CS reduces the risk of local recurrence to approximately 10%, half of these recurrences (5%) are invasive for a potential long-term cure rate of 95%. Several randomized trials comparing CS with or without radiation therapy (RT) are in progress. The factors that increase the rate of local recurrence after CS alone for DCIS include close or involved margins, and the presence of necrosis or high-grade tumours. Patients with these features should have radiation therapy if breast conservation is preferred. Patients with low-grade tumours (without necrosis) up to 15 mm, with clear margins of at least 10 mm, who agree to be closely observed may be good candidates for CS alone. A critical review of the literature is presented.

Ductal carcinoma in situ. Part I: Definition and diagnosis.

The frequency of diagnosis of ductal carcinoma in situ (DCIS) has increased in Australia, largely because of the national screening programme. Ductal carcinoma in situ presents a dilemma because of problems with its diagnosis and variations in reporting pathological and radiological findings, making it difficult to define optimal treatment and communicate information in a way that helps the patient understand the problems and make decisions. There is considerable inter-observer variation, particularly in differentiating low-grade DCIS from ductal hyperplasia, with or without atypia, but pathologists who participate in regular pathological review sessions vary less in their opinions. Mammography remains the main investigative tool for DCIS and the American College of Radiology has recommended standardized reports. A team approach is required for the removal and diagnosis of possible DCIS. Although the team may be best co-located in the one facility, this is not practical in many community hospital settings which lack on-site radiology and pathology services. The decision about how much breast tissue to remove will need to be made for each patient and depends on the size of the microcalcification and how suspicious the mammogram is for DCIS. We recommend the use of synoptic reports for DCIS, and we document the minimum factors that should be reported by pathologists. The evaluation and management of DCIS by a multidisciplinary team will allow the patient access to information required to make often difficult treatment decisions. In this paper, we review the literature about the natural history, pathology, cytology and radiology of DCIS and document the 20 critical steps required for the diagnosis of impalpable, mammographic microcalcifications suspected to be DCIS.

Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.

PURPOSE: This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (> 10 nodes, 45 patients; or > or = 70% involved nodes, if < 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy. PATIENTS AND METHODS: Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS: One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths. CONCLUSION: Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.