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Umberto Veronesi

Publications and source records attributed to Umberto Veronesi.

At least 55 records · Page 3Linked to original sources

Relationships between plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3 and second breast cancer risk in a prevention trial of fenretinide.

PURPOSE: High circulating insulin-like growth factor (IGF) -I and/or low IGF-binding protein (IGFBP) -3 levels are associated with increased breast cancer risk in unaffected premenopausal women. We determined whether IGF-I and IGFBP-3 predict second breast cancer risk, and whether their changes during fenretinide explain observed reductions in second breast cancer in women </=50 years of age. EXPERIMENTAL DESIGN: Within a Phase III trial, we measured baseline and 1-year levels of IGF-I, IGFBP-3, and their ratio in 302 subjects on fenretinide and 220 controls who provided plasma samples. The prognostic effect of IGF-I and IGFBP-3, and the surrogate effect of IGF-I during fenretinide were assessed by Cox models after 9.4 years. RESULTS: Among controls, high IGF-I and low IGFBP-3 were associated with elevated second breast cancer risk [top versus bottom tertile, IGF-I, hazard ratio (HR) = 1.94, 95% confidence interval (CI), 0.87-4.31, P = 0.105; and IGFBP-3, HR = 0.40, 95% CI, 0.18-0.93, P = 0.033]. Fenretinide induced reductions of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 of 8% (95% CI, 2-12%; P = 0.004), 3% (95% CI, 1-5%; P = 0.002), and 5% (95% CI, 0-10%; P = 0.050), respectively. Second breast cancer risk was reduced by 39% (HR = 0.61; 95% CI, 0.40-0.94; P = 0.026). The percentage of treatment effect explained by IGF-I and IGF-I:IGFBP-3 reductions were 4.8% (95% CI, 0.8-28.9%) and 3.1% (95% CI, 0.5-20.8%), respectively. CONCLUSIONS: Fenretinide induced a moderate reduction of IGF-I, which marginally explains observed cancer risk reductions in women </=50 years of age. In this age group high IGF-I and particularly low IGFBP-3 levels predict second breast cancer risk.

Adult↗

A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.

BACKGROUND: Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. METHODS: From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). RESULTS: The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. CONCLUSIONS: Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer.

Adult↗

A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers.

BACKGROUND: Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. METHODS: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. RESULTS: Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P =.81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. CONCLUSIONS: The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.

Adult↗

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women.

Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.

Antineoplastic Agents, Hormonal↗

Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery.

HYPOTHESIS: The current standard treatment for early breast cancer includes conservative surgery followed by entire breast radiotherapy (RT). Recent study findings show that most local recurrences are in the scar tissue area suggesting that whole-breast RT may not always be necessary. If the volume of breast tissue to be irradiated is limited, RT may be performed intraoperatively. Intraoperative RT delivered with electrons at the total isodose of 2100 rad (21 Gy) could in principle substitute the currently used radiation course of external RT after breast-conserving surgery in selected cases. PATIENTS AND METHODS: We report our findings on intraoperative RT using a specially designed mobile linear accelerator delivering 4 energy levels of electrons (3, 5, 7, and 9 MeV) via a head maneuvered by a robot arm. We applied this technique to 237 patients with breast cancer (mean age, 59 years; age range, 33-80 years) with tumors smaller than 2 cm in maximum diameter (T1); most underwent wide resection and an axillary sentinel node biopsy. RESULTS: After a median follow-up of 19 months (range, 7-33 months), the rate of posttreatment complications is very low. Four patients (1.7%) developed breast fibrosis-mild in 3 patients and severe in 1 patient-that resolved in 24 months. Three patients (1.4%) developed ipsilateral breast cancer-2 (1.0%) contralateral breast cancer, 1 (0.5%) supraclavicular node metastasis, and 1 (0.5%) distant metastases. CONCLUSIONS: Intraoperative RT with electron beams reduces irradiation to the skin, subcutaneous tissue, and contralateral breast and lung. It appears to be a promising method for irradiating conservatively treated breasts and it avoids the long period of postoperative RT that may not be easily accessible to all patients.

Adenocarcinoma↗

Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast.

HYPOTHESIS: A sentinel lymph node (SLN) biopsy should not be considered a standard procedure in the treatment of all patients with ductal carcinoma in situ (DCIS) of the breast if the lesion is completely excised by radical surgery and there are free margins of resection. DESIGN: Prospective case series. SETTING: Department of breast surgery of a comprehensive cancer center. PATIENTS: From January 1, 1998, to December 1, 2001, 223 unselected consecutive patients affected by pure DCIS of the breast underwent an SLN biopsy. RESULTS: Metastases in the SLN were detected in 7 (3.1%) of the 223 patients, and complete axillary dissection was subsequently performed in all these patients but 1. Of these 7 patients, 5 had only micrometastases in the SLNs; and in the 6 patients treated with complete axillary dissection, the SLN was the only positive node. CONCLUSIONS: Because of the low prevalence of metastases, an SLN biopsy should not be considered a standard procedure in all patients with DCIS. In patients with pure DCIS in whom the lesion is completely excised by radical surgery, an SLN biopsy could be avoided. It could be considered in patients with DCIS undergoing mastectomy, in whom there exists a higher risk of harboring an invasive component using definitive histologic features, like large solid tumors or diffuse or multicentric microcalcifications; in these patients, an SLN biopsy cannot be performed at a later operation. Complete axillary dissection may not be mandatory if the SLN is micrometastatic.

Adult↗

HRT opposed to low-dose tamoxifen (HOT study): rationale and design.

The rationale for the HOT study is mainly based on the findings of the Italian Tamoxifen Prevention Study, where 5,408 healthy hysterectomized women aged 35-70 years were randomized to 20 mg/day of tamoxifen or placebo for 5 years. After 81.2 months median follow-up, 79 breast cancers occurred (34 on tamoxifen versus 45 on placebo, p=0.215). In the subgroup of 1,580 women who used estrogen replacement therapy (ERT) at some point during the study, 23 breast cancers were observed: 17 on placebo and 6 on tamoxifen (hazard ratio=0.35, 95% CI, 0.14-0.89). Pharmacokinetic and pharmacodynamic (surrogate endpoint biomarkers) studies showed that a lower dose of tamoxifen (such as 5 mg/day) does not affect the drug's activity on several biomarkers of both cardiovascular and breast cancer risk. We therefore propose a multicenter placebo-controlled phase III trial in postmenopausal healthy women on hormone replacement therapy (HRT) to assess whether the combination of HRT and low-dose tamoxifen retains the benefits while reducing the risks of either.

Breast Neoplasms↗

In vivo dosimetry using radiochromic films during intraoperative electron beam radiation therapy in early-stage breast cancer.

BACKGROUND AND PURPOSE: To check the dose delivered to patients during intraoperative electron beam radiation therapy (IOERT) for early breast cancer and also to define appropriate action levels. PATIENTS AND METHODS: Between December 2000 and June 2001, 54 patients affected by early-stage breast cancer underwent exclusive IOERT to the tumour bed using a Novac7 mobile linac, after quadrantectomy. Electron beams (5, 7, 9 MeV) at high dose per pulse values (0.02-0.09 Gy/pulse) were used. The prescribed single dose was 21 Gy at the depth of 90% isodose (14-22 mm). In 35 cases, in vivo dosimetry was performed. The entrance dose was derived from the surface dose measured with thin and calibrated MD-55-2 radiochromic films, wrapped in sterile envelopes. Films were analysed 24-72 h after the irradiation using a charge-coupled-device imaging system. Field disturbance caused by the film envelope was negligible. RESULTS: The mean deviation between measured and expected doses was 1.8%, with one SD equal to 4.7%. Deviations larger than 7% were found in 23% of cases, never consecutively, not correlated with beam energy or field size and with no evidence of linac daily output variation or serious malfunctioning or human mistake. The estimated overall uncertainty of dose measurement was about 4%. In vivo dosimetry appeared both reliable and feasible. Two action levels, for unexplained observed deviations larger than 7 and 10%, were preliminary defined. CONCLUSIONS: Satisfactory agreement between measured and expected doses was found. The implementation of in vivo dosimetry in IOERT is suggested, particularly for patients enrolled in a clinical trial.

Breast Neoplasms↗

Sentinel lymph node metastasis in microinvasive breast cancer.

BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM) is a separate pathological entity, distinct from pure ductal carcinoma in situ (DCIS). DCISM is a true invasive breast carcinoma with a well-known metastatic potential. Currently, there is controversy regarding the indication for complete axillary dissection (CAD) to stage the axilla in patients with DCISM. The role of CAD is questioned given its morbidity and reported low incidence of axillary involvement. Sentinel lymph node biopsy (SLNB) may obviate the need for CAD in these patients without compromising the staging of the axilla and the important prognostic information. METHODS: From March 1996 to December 2002, 4602 consecutive patients with invasive breast carcinoma underwent SLN biopsy. Of these, 41 patients with DCISM were selected. RESULTS: Metastasis in the SLN were detected in 4 of 41 (9.7%) patients. Two of the 4 patients had only micrometastasis in the SLN. In three patients, the SLN was the only positive node after CAD. CONCLUSIONS: SLN biopsy should be considered as a standard procedure in DCISM patients. SLNB can detect nodal micrometastasis and accurately stage the axilla avoiding the morbidity of a CAD. Complete AD may not be mandatory if only the SLN contains micrometastatic disease. Informed consent is very important in the decision not to undergo CAD.

Axilla↗

Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome.

OBJECTIVES: To assess, in women participating in a breast cancer prevention trialon fenretinide (4-HPR), the relationship of drug and retinol levels with the risk of second breast malignancy, taking into account age and menopausal status. METHODS: In a multicenter prevention trial, women with early breast cancer were randomly assigned to receive no treatment or 200 mg of 4-HPR/day for 5 years. Blood was collected at baseline and on a yearly basis during intervention from women recruited at the Istituto Tumori (Milan, Italy; 818 and 756 in the 4-HPR and control arm, respectively, who accounted for 53% of the participants in the trial). The plasma concentrations of 4-HPR, its main metabolite N-(4-methoxyphenyl) retinamide, and retinol were assayed by high-performance liquid chromatography. Three age ranges ( or=56 years), menopausal status at baseline, and disease outcome at a median follow-up of 97 months were taken into account in the analysis. RESULTS: Baseline retinol levels were significantly lower (P or=46 years versus or= 0.71; P <or= 0.001) related to pretreatment retinol levels. CONCLUSIONS: Retinol plasma levels increased with age and after menopause and were not related to breast cancer recurrence. 4-HPR levels were lower in subjects < 45 years than in older subjects. The inverse relationship between drug plasma levels and 4-HPR preventive effects observed in young women suggests a role for 4-HPR plasma sequestration in 4-HPR biological activity.

Adult↗

Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.

BACKGROUND: We conducted 20 years of follow-up of women enrolled in a randomized trial to compare the efficacy of radical (Halsted) mastectomy with that of breast-conserving surgery. METHODS: From 1973 to 1980, 701 women with breast cancers measuring no more than 2 cm in diameter were randomly assigned to undergo radical mastectomy (349 patients) or breast-conserving surgery (quadrantectomy) followed by radiotherapy to the ipsilateral mammary tissue (352 patients). After 1976, patients in both groups who had positive axillary nodes also received adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. RESULTS: Thirty women in the group that underwent breast-conserving therapy had a recurrence of tumor in the same breast, whereas eight women in the radical-mastectomy group had local recurrences (P<0.001). The crude cumulative incidence of these events was 8.8 percent and 2.3 percent, respectively, after 20 years. In contrast, there was no significant difference between the two groups in the rates of contralateral-breast carcinomas, distant metastases, or second primary cancers. After a median follow-up of 20 years, the rate of death from all causes was 41.7 percent in the group that underwent breast-conserving surgery and 41.2 percent in the radical-mastectomy group (P=1.0). The respective rates of death from breast cancer were 26.1 percent and 24.3 percent (P=0.8). CONCLUSIONS: The long-term survival rate among women who undergo breast-conserving surgery is the same as that among women who undergo radical mastectomy. Breast-conserving surgery is therefore the treatment of choice for women with relatively small breast cancers.

Antineoplastic Combined Chemotherapy Protocols↗

Sentinel lymph node biopsy performed with local anesthesia in patients with early-stage breast carcinoma.

HYPOTHESIS: Sentinel lymph node (SN) biopsy performed with local anesthesia has a positive effect on patients' quality of life and on treatment management for early-stage breast carcinoma. This method represents an interesting development in breast-conserving surgery. DESIGN: We performed SN biopsy with local anesthesia in selected patients to test the feasibility of the technique and its impact on our organization and on patients' quality of life. PATIENTS AND METHODS: From September 2000 to December 2001, we studied 115 patients with a palpable breast tumor (maximum diameter, 2.5 cm). The axilla was clinically negative for metastasis in all cases. RESULTS: Forty-eight patients (41.7%) had SNs that were positive for metastasis. In 20 cases (17.4%), the SN was macrometastatic and in 28 cases (24.3%), it was micrometastatic (diameter <2 mm). The SN was negative for metastasis in 66 cases (57.4%). In 1 case, the histologic examination revealed the presence of a non-Hodgkin B-cell lymphoma. The complete axillary dissection performed in the subgroup of patients with macrometastatic SNs showed that in 9 cases (45%), the SN was the only positive node. In another 9 cases (45%), patients had fewer than 4 positive axillary lymph nodes; more than 4 axillary nodes were metastatic in 2 cases (10%). Among the 28 patients with SN micrometastasis, 21 received complete axillary dissection: 15 patients (53.6%) had no other metastasis to the axillary nodes and 6 patients (21.4%) had cancer cells in other axillary nodes. In case of micrometastasis, we suggested that patients enter the International Breast Cancer Study Group 2301 trial (15 of them accepted and signed the informed consent), which compared completion of axillary dissection with no further surgical treatment of the axilla. Based on randomization, 7 patients (25%) in the group with micrometastasis to the SN received no axillary dissection. Patients' tolerance to this kind of treatment was excellent. CONCLUSION: Our experience indicates that SN biopsy performed with local anesthesia can be a suitable alternative to standard intraoperative evaluation with general anesthesia in patients with unifocal, early-stage breast carcinoma.

Anesthesia, Local↗

Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer.

At the European Institute of Oncology, Milan, Italy, we have focused our interest on the use of intraoperative radiation therapy (IORT) in limited-stage breast cancer that is conservatively treated. A new technique to perform IORT was applied in 185 patients from July 1, 1999, to October 31, 2001. As the surgeon plays a crucial role in this procedure in selecting the patients, performing the breast resection, preparing the gland as a target to receive IORT, delivering the radiation directly to the mammary gland via a dedicated applicator, and, finally, reconstructing the breast, each phase of the surgical technique has been completely standardized and is described herein. The use of IORT in the conservative treatment of breast cancer could allow the course of external fractionated-dose radiation therapy to be completely avoided; IORT dramatically reduces radiation exposure of the skin, lung, and subcutaneous tissues and avoids the irradiation of the contralateral breast, which contributes to a very low incidence of radiation-induced sequelae. In our experience, IORT for limited-stage breast carcinoma is easy to perform and only briefly prolongs the duration of the surgical procedure.

Breast Neoplasms↗

Effect of fenretinide on ovarian carcinoma occurrence.

OBJECTIVE: The aim of this study was to update the effect of fenretinide, a synthetic vitamin A analogue proposed for chemoprevention, on the occurrence of ovarian carcinoma. METHODS: Data were obtained from a randomized clinical trial for the prevention of second breast cancer. For the present investigation, events of interest were new primary carcinomas of the ovary arising in the fenretinide or the no-treatment (control) arm. The probability of carrying a BRCA germ-line mutation was assessed in women with ovarian carcinoma according to G. Parmigiani et al. (1998, Am J Hum Genet 62, 145-58). RESULTS: Fenretinide reduced ovarian carcinoma occurrence during the 5-year intervention period (0 versus 6 cases in the fenretinide and control arm, P = 0.0327). This effect was no longer evident after the 5-year intervention period (6 versus 4 cases, P = 0.7563). Therefore with median observation time of 121 months, a total of 6 carcinomas of the ovary occurred in the fenretinide group and 10 in the control group. The probability of carrying a BRCA mutation was lower for women with ovarian carcinoma in the treatment arm. CONCLUSION: Fenretinide treatment was associated with a lower incidence of ovarian carcinoma during the intervention period but such a protective effect seems to disappear after treatment. Furthermore, a possible protective effect of fenretinide in BRCA-mutated women was suggested. Further studies on fenretinide for the prevention of ovarian carcinoma particularly in women with genetic susceptibility appear necessary.

Adult↗

Axillary radiotherapy instead of axillary dissection: a randomized trial. Italian Oncological Senology Group.

BACKGROUND: Surgical dissection of the axilla is a standard part of the treatment of breast cancer but, by itself, does not improve prognosis; furthermore, most patients with small-sized breast cancer and a clinically uninvolved axilla never develop axillary metastases. We evaluated disease-free and overall survival in patients with early breast cancer treated by breast-conservation surgery without dissection of axillary lymph nodes, receiving or not receiving axillary radiotherapy (RT). METHODS: From 1995 to 1998, 435 patients older than 45 years with breast cancer up to 1.2 cm were randomized, 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. RESULTS: After a follow-up of 28 to 68 months (median, 42 months), two women (1%) in the no axillary treatment group and one (.5%) in the axillary RT group developed axillary metastases. Rates of distant metastases and local treatment failure were also very low, and 5-year overall survival was 99%. CONCLUSIONS: After a mean of 46 months of follow-up, our results indicate that axillary dissection can be safely avoided in patients with very small invasive carcinomas and a clinically negative axilla. Whether axillary RT should be added can be assessed only by longer follow-up.

Axilla↗

Stage migration after biopsy of internal mammary chain lymph nodes in breast cancer patients.

BACKGROUND: Involvement of the internal mammary chain lymph nodes (IMNs) is associated with worsened prognosis in breast cancer. Use of lymphoscintigraphy to visualize sentinel nodes reveals that IMNs often receive lymph from the area containing the tumor. METHODS: We biopsied IMNs in 182 patients because there was radiouptake to the IMNs or because the tumor was located in the medial portion of the breast. After tumor removal, pectoralis major fibers were divided to expose intercostal muscle. A portion of intercostal muscle adjacent to the sternum was removed. Lymph nodes and surrounding fatty tissue in the intercostal space were freed, removed, and analyzed histologically. The pleural cavity was breached in four cases (2.2%), with spontaneous resolution. RESULTS: IMNs were found in 160 (88%) of 182 patients; 146 (94.4%) were negative and 14 (8.8%) were positive. The latter received internal mammary chain radiotherapy. The axilla was negative in 4 of 14 cases and positive in 10. CONCLUSIONS: IMNs can be quickly and easily removed via the breast incision with insignificant risk and no increase in postoperative hospitalization. The patients with a positive IMN migrated from N0 (4 cases) or N1 (10 cases) to N3, prompting modification of both local (radiotherapy to internal mammary chain) and systemic treatment; without IMN sampling, they would have been understaged.

Breast Neoplasms↗