The applicability of Magseed® for targeted axillary dissection in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of sentinel node biopsy alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NAC). However methods for TAD are still under investigation. METHODS: Magseed®, a non-radioactive magnetic marker was used to mark the biopsied positive TLN after NAC. The SLNB with the standard technetium-based method and the selective TLNB with Magseed® localization were performed in 40 patients. The TLNs were identified with the Sentimag® probe and excised in all patients. Specimen x-ray was performed to confirm the Magseed® within the prior to NAC biopsied and clipped lymph node. RESULTS: The TLN identification rate was 100% (40/40), the SLN identification rate was 82.5% (33/40), the concordance rate between the TLN and the SLN was 65% (26/40). Complications according Magseed® deployment or identification could not be observed. CONCLUSION: Magseed® is a reliable and feasible marker for the identification of TLNs after NAC.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials.

Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab.

BACKGROUND: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. PATIENTS AND METHODS: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. RESULTS: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). CONCLUSIONS: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.

Residual specimen cellularity after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for breast cancer reduces tumour cellularity, the percentage of the primary tumour area that is composed of invasive tumour cells. Minimal residual tumour cellularity (5 per cent or less of tumour area composed of invasive tumour cells) may be associated with an increased risk of false-negative intraoperative margins. The aim of this study was to evaluate the incidence of minimal residual tumour cellularity after neoadjuvant chemotherapy and its impact on the frequency of false-negative margins and conversion from breast-conserving surgery to mastectomy. METHODS: The final pathology slides of 510 patients who had surgery after neoadjuvant chemotherapy were reviewed. RESULTS: Of 396 patients with residual invasive breast cancer after neoadjuvant chemotherapy, 100 specimens (25.3 per cent) had minimal residual cellularity; this was more frequent in patients with invasive lobular carcinoma (17.0 versus 5.1 per cent; P < 0.001) or well and moderately differentiated carcinoma (68.0 versus 52.4 per cent; P = 0.007). Among 149 patients who had initial breast-conserving surgery, false-negative intraoperative margin rates were 23 per cent in specimens with minimal and 13.8 per cent in those with higher residual cellularity (P = 0.210). There was no significant difference in the rate of conversion to mastectomy between the groups. CONCLUSION: Minimal residual cellularity after neoadjuvant chemotherapy occurred in about 25 per cent of specimens, but did not alter the rate of false-negative intraoperative margins.

Retrospective comparison of chemotherapy-induced myelotoxicity in patients with ovarian cancer under and over 60 years of age.

We examined whether women aged 60 years or older with ovarian cancer who were treated with surgery and postoperative chemotherapy are at higher risk of developing grade 4 hematological toxicity. Seventy-five patients were included: 34 patients aged < 60 years (group I) were compared with 41 patients aged > or =60 years (group II) after postoperative treatment with single-agent carboplatin or carboplatin/taxane combination chemotherapy. Secondary prophylaxis with granulocyte colony-stimulating factors was performed to avoid dose reduction and chemotherapy delay. A total of 450 chemotherapy cycles was completed. Anemia and thrombocytopenia were mild in both groups. Overall, grade 4 neutropenia developed in 41% (group I) and in 49% (group II) (p=0.51). Febrile neutropenia occurred in 12% and 2%, respectively (p=0.17). The carboplatin/taxane combination was associated with grade 4 neutropenia in 42% (group I) and 58% (group II) (p=0.21). Women > or =60 years are not at higher risk of developing severe myelotoxicity than their younger counterparts, particularly after treatment with carboplatin/taxane combination chemotherapy.

200 Sentinel lymph node biopsies without axillary lymph node dissection -- no axillary recurrences after a 3-year follow-up.

The aim of this study is to evaluate the rate of axillary recurrences in sentinel lymph node (SLN)-negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Between May 1999 and February 2002, 333 consecutive patients with primary invasive breast cancer up to 4 cm and clinically negative axillae were entered into this prospective study. Sentinel lymph nodes were identified using the combined method with blue dye (Patent blue V) and technetium 99m-labelled albumin (Nanocoll). Sentinel lymph nodes were examined by frozen sections, standard haematoxylin and eosin staining and immunohistochemistry staining. In SLN-positive patients, ALND was performed. Sentinel lymph node-negative patients had no further ALND. The SLN identification rate was 98.5% (328 out of 333). In all, 128 out of 328 (39.0%) patients had positive SLNs and complete ALND. A total of 200 out of 328 (61.0%) patients were SLN negative and had no further ALND. The mean tumour size of SLN-negative patients was 16.5 mm. The mean number of SLNs removed was 2.1 per patient. There were no local or axillary recurrences at a median follow-up of 36 months. The absence of axillary recurrences after SLNB without ALND in SLN-negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity than ALND. Short-term results are very promising that SLNB without ALND in SLN-negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumours.

Comparison of quality of life and arm complaints after axillary lymph node dissection vs sentinel lymph node biopsy in breast cancer patients.

The sentinel lymph node biopsy (SLNB) represents a minimal invasive surgical method for axillary staging in patients with primary breast cancer. In a prospective study, evaluation of quality of life (QOL) and arm morbidity was performed before surgery on a total of 56 breast cancer patients. The EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires were used for QOL assessment. Assessment of pain was additionally observed using the McGill Pain Questionnaire. Arm mobility was observed by goniometric measurement of arm movement. Data were collected before surgery (t1), 1 week after discharge (t2) and 9-12 months after surgery (t3). The type of axillary surgery does not seem to affect global QOL at a short-time follow-up, but patients recover sooner after SLNB. Body image and sexual functioning remain stable in both types of axillary surgery. Arm/shoulder pain was reported in 36% of patients after SLNB in comparison to 68% receiving axillary lymph node dissection (ALND), and 'numbness' was reported only in 4% of patients in the SLNB group vs 19.3% after ALND. Abduction, flexion and horizontal adduction of the affected arm show significant impairment after ALND. Breast cancer patients should be counselled about the benefits of SLNB over ALND concerning QOL and postsurgery side effects in a short-term follow-up.

Sentinel lymph node biopsy alone without axillary lymph node dissection--follow up of sentinel lymph node negative breast cancer patients.

AIMS: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). METHODS: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. RESULTS: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03+/-1.22. Mean tumor size was 17.15+/-7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12+/-6.38 months. CONCLUSION: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.

[Sentinel lymph node biopsy in breast cancer patients--results and experience after 500 sentinel lymph node biopsies]. / Die Sentinellymphknotenbiopsie beim Mammakarzinom. Ergebnisse und Erfahrungen nach 500 Sentinellymphknotenbiopsien.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a widely used technique for axillary staging in breast cancer patients. The principle to evaluate the axillary status of a breast cancer patient with a less invasive surgery than axillary lymph node dissection (ALND) meets the new minimally invasive concept in breast cancer surgery. Some breast cancer centers proceed to SLNB without ALND in SLN-negative patients. PATIENTS AND METHODS: Between March 1998 and March 2002, 500 SLNBs were performed. After a learning period with SLNB and ALND in 75 patients with a sensitivity of 96.2% and a false-negative rate of 3.8%, SLNB alone without further ALND was performed in a group of patients. In addition, the feasibility of SLNBin patients with locally advanced breast cancer, in patients after neoadjuvant chemotherapy and in patients with multicentricity was evaluated. The combined method with blue dye and technetium-99m-labeled human albumin for identification of SLNs was applied. RESULTS: 500 SLNBs were performed. The identification rate was 86.2%. After exclusion of patients with neoadjuvant chemotherapy and patients with multicentricity, the identification rate was 94.5%. SLNs were positive in 41.3% of patients and negative in 58.7% of patients. DISCUSSION: SLNB is an excellent method for axillary stag-ing and an alternative for ALND in a certain group of breast cancer patients.

Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients.

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.

Prospective assessment of quality of life of female cancer patients.

OBJECTIVE: The aims of this study were to compare the quality of life (QOL) of women with different cancer sites; to identify predictors of QOL; and to examine the agreement between patient self-reported QOL and QOL ratings provided by clinicians and significant others. METHODS: A prospective study was conducted including 248 patients with gynecologic and breast cancer. QOL data were collected at six time points before, during, and after treatment, using the EORTC QLQ-C30 and the Spitzer QL index (QL-I). RESULTS: Baseline assessments showed comparable QOL scores among patients with different gynecologic malignancies and breast cancer. During active treatment breast cancer patients had significantly higher mean scores in physical functioning compared to women with gynecologic cancers and higher scores in role functioning compared to patients with cervical cancer. After completion of treatment there were no statistically significant differences in QOL among the groups. For all women, global QOL and emotional functioning were mostly affected during and after treatment. Regression analysis showed that patients' global QOL was significantly predicted by severity of surgery (t = 3.903, P < 0.01) and pretreatment performance status (t = 3.116, P = <0.01). Comorbidity, family support, number of treatments, age, and stage of disease were not predictive. The comparison of patient self-rated QOL and observer-rated QOL showed that the QL-I mean scores of health providers and relatives were generally in close agreement with those of patients. Intraclass correlations were moderate to high during active treatment and excellent after completion of treatment. CONCLUSION: In female cancer patients, global QOL and emotional functioning are mostly affected during the course of disease, independent of their diagnosis. Significant others and health professionals are able to provide useful information on QOL of patients recovering from cancer.