Nipple Preservation Research Articles

Immediate Nipple Reconstruction with Autologous Breast Reconstruction Following Areola-Sparing Mastectomy

INTRODUCTION: Areola-sparing mastectomy preserves the specialized areola skin, the subtleties of which are difficult to reconstruct, but avoids oncologic concerns associated with nipple preservation.1 Autologous breast reconstruction provides skin to reconstruct the nipple in the immediate setting. This study evaluates the technique, reliability and aesthetic outcome of immediate nipple reconstruction in the setting of areola-sparing mastectomy. METHODS: Forty out of 521 free flap breast reconstructions (32 DIEP flaps, 6 TUG flaps, 2 PAP flaps) in 21 patients, who were followed prospectively from 02/2010 to 02/2014 were done following areola-sparing mastectomies. The procedure was indicated based on the breast surgeons’ preferences and aesthetic considerations (areola position, skin envelope, breast volume). Mastectomy incisions were designed around the nipple with a 4-6cm inferior vertical extension. An inferiorly based modified CV-flap utilizing skin of the underlying free flap was used for nipple reconstruction, which was done delayed in the first 2 reconstructions and immediate in the remaining 38. A temporary skin island inset into the inferior pole incision for postoperative monitoring was excised 2-3 weeks postoperatively. RESULTS: Flap success rate was 100%. Viability of the reconstructed nipples was 100% in all cases. One patient had partial areola skin loss with secondary healing. Nipple projection was sufficient in all cases. Revision of the nipple inset was done in 2/38 immediate reconstructions. Preservation of the areola with its subtle coloration, texture, and soft transition to the surrounding breast skin provided favorable aesthetic results compared to periareolar incisions (Figures 1 and 2).Figure 1: Preoperative appearance.Figure 2: Postoperative appearance after areola-sparing mastectomy, DIEP flap and immediate nipple reconstruction.CONCLUSION: Immediate nipple reconstruction in the setting of areola-sparing mastectomy can be performed safely, with less risk of tissue loss compared to reports of nipple-sparing mastectomy.2 Supple tissue characteristics in the immediate setting facilitate the inset and minimize scarring around the reconstructed nipple compared to delayed nipple reconstruction. The procedure should be considered when nipple-preservation is not performed in patients with appropriate areola position, and may provide excellent aesthetic results with the potential for single-stage autologous breast reconstruction.

Impact of nipple preservation on implant-based reconstruction outcome

Journal of the American College of Surgeons: October 2014 - Volume 219 - Issue 4 - p e133 doi: 10.1016/j.jamcollsurg.2014.07.741

Outcome of the use of acellular-dermal matrix to assist implant-based breast reconstruction in a single centre

IntroductionThe use of acellular dermal matrix (ADM) has transformed the technique of implant-based breast reconstruction. It offers the option of a one-stage procedure and is felt to have benefits in cosmetic outcome but the medium and long-term outcomes are unknown. MethodsAll cases where ADM was used in a breast reconstructive procedure in the Edinburgh Breast Unit from its initial use on 7/7/2008 to 31/7/2012 were reviewed retrospectively. Follow up was completed to 30/11/2012. Results147 patients received 232 sheets of ADM (156 Strattice, 73 Permacol and 3 Alloderm). Mean follow up was 687 days. In 40 cases unplanned implant explantation occurred (17.2% or 27.2% of patients). 7 of 27 (25.9%) patients requiring adjuvant therapy had this delayed due to problems with the reconstruction. 30 of 80 patients (37.5%) undergoing unilateral surgery have undergone contralateral surgery. Implant loss varied significantly with smoking (34.6% loss rate in smokers vs 13.2% in non-smokers, p = 0.001), with radiotherapy (28.1% loss rate vs 13.8% with no radiotherapy, p = 0.001) and with incision type. There was no statistically significant variation by operating surgeon, type of ADM used, chemotherapy use, patient weight, breast weight or nipple preservation. Patients underwent a mean of 1.54 further operations (range 0–7). ConclusionsWhile offering potential cosmetic and financial benefits, the use of ADM with implant-based reconstructions has a significant rate of implant loss, further surgery and potential delay in adjuvant therapy. These must be considered when planning treatment and consenting patients.

Experience with nipple-sparing mastectomy after prior whole-breast radiation.

173 Background: Nipple-sparing mastectomy (NSM) is being performed more frequently for risk reduction and breast cancer treatment. Prior whole breast irradiation (WBI) has been considered a contraindication to NSM. This study reviews our NSM experience following prior WBI. Methods: We reviewed our prospective mastectomy database from April 2007 to April 2012 for patients undergoing NSM. Ten patients out of a total 169 NSM were identified that underwent NSM following prior WBI. Data collected included incision type, follow-up, complications, cosmesis, and recurrence. Results: Of the ten NSM patients who received prior WBI, 6 had recurrent ipsilateral breast cancer at the lumpectomy site, 3 developed contralateral breast cancers and opted for bilateral NSM, and 1 patient opted for bilateral NSM after finding a BRCA mutation following BCT. Mean patient age was 53. Two patients had comorbities: 1 hyperlipidemia and 1 former smoker. Three of 10 (30%) developed complications, with 2 partial necrosis of nipple-areola complex (NAC) and 1 complete loss of the NAC (Table). No patient required return to the operating room (local resection in the office was performed for the complete NAC loss) and all patients had good final cosmesis. All patients underwent immediate reconstruction: 5 tissue expanders (TE), 2 DIEP and 3 TRAM flaps. Mean follow up is 23 months with no local recurrences to date. Conclusions: This study demonstrates that NSM with immediate reconstruction can be performed in selected patients with prior WBI with an acceptable rate of nipple preservation and good cosmesis. NAC preservation is the ultimate goal in patients undergoing NSM. Current studies are ongoing to identify risk factors that may be associated with nipple necrosis. [Table: see text]

Conservative mastectomy: extending the idea of breast conservation

Conservative mastectomy is a surgical technique to remove breast glandular tissue without disruption to the appearance of the breast. The main contraindication to this operation is involvement of the nipple-areola complex. Preservation of a healthy nipple does not affect long-term survival rates. Intraoperative retroareolar biopsy and accurate removal of all mammary tissue are mainstays to guarantee oncological safety of the technique. A complication, however infrequent, is nipple necrosis, which can be treated successfully by local excision. Several breast reconstructive techniques are used during conservative mastectomy and aesthetic results are good in most cases.

Comparison of Patient Characteristics and Outcomes of Contralateral Prophylactic Mastectomy and Unilateral Total Mastectomy in Breast Cancer Patients

There has been an increasing trend toward contralateral prophylactic mastectomy (CPM) in the management of breast cancer (BCa). This study's objective was to compare clinicopathologic characteristics of BCa patients who elected CPM to those who elected unilateral total mastectomy (UTM) and to determine whether CPM improved survival. Comparison was performed on 355 patients with stage 0-III BCa matched by age and stage who underwent mastectomy from 1995 to 2008: 177 patients had CPM; 178 patients had UTM. Clinicopathological characteristics and survival outcomes were analyzed. Women who underwent preoperative MRI were twice as likely to have CPM (40.9 vs. 19.7%, P < 0.001). MRI identified additional suspicious foci in 45% CPM and 19% UTM. Patients with history of previous breast biopsies, family history, or BRCA mutation were more likely to choose CPM than UTM (40.1 vs. 24%, P = 0.001; 64.3 vs. 41.4%, P < 0.001; 20.3 vs. 6.5%, P = 0.04, respectively). CPM patients elected nipple preservation (26 vs. 5.2%, P < 0.001) and immediate reconstruction more often (92.2 vs. 73.5%, P < 0.001); UTM patients were more likely to have attempted breast conservation prior to mastectomy (52.8 vs. 39.5%, P = 0.01). CPM identified occult BCa in 11 patients (6.6%), and three UTM patients (1.7%) developed contralateral BCa. With median follow-up of 61 months, by univariable/multivariable analyses, CPM did not improve overall, disease-free, or distant metastases-free survival. Factors that may influence choice of CPM included preoperative MRI, history of prior breast biopsies, immediate reconstruction, nipple preservation, family history, and BRCA status. Those who chose CPM did not have improved survival.

P2-16-16: Nipple Sparing Mastectomy and Immediate Breast Reconstruction: Critical Appraisal of Five Year, Single Centre Outcomes.

Abstract Background Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom ( 2:1 ratio of immediate versus delayed respectively). Whilst skin sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple preservation remains controversial. In over 1,800 peer reviewed nipple sparing mastectomy (NSM) cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease free survival. This study aims to evaluate in a selected cohort of patients, the oncological safety and aesthetic outcome of nipple- sparing mastectomy and immediate breast reconstruction (IBR). We highlight the surgical technique used and propose in/exclusion criteria. Material and Methods: Patients were identified retrospectively from our Institution's electronic patient records and WinPath™ database by searching clinical codes corresponding to NSM &amp; IBR, performed by the senior authors (IJL and RD) between January 2004 and December 2008. Pre-operative selection criteria included: 100% pre-operative lesion characterisation; 5mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved/close margins. Follow-up data was verified from patients’ case notes, histo- pathological review and standardised photographic views. Endpoints include: local recurrence rate, disease free survival, peri-operative NAC subcutaneous tissue loss and validated aesthetic outcome measures. Results*: 84 patients underwent NSM &amp; IBR for invasive disease. The mean age was 52.1 years and a median follow-up of 38 months. IBR utilised autologous tissue (latissimus dorsi or transverse rectus abdominus musculocutaneous flaps) with/without implant prosthesis. There was one case of local recurrence (1.2%) in a patient who declined re-excision of close/involved margins and no recorded breast cancer related deaths. Peri-operative complication rates were within the national mastectomy breast reconstruction audit outcome guidelines. Conclusion: In this cohort of patients, nipple sparing mastectomy and immediate breast reconstruction achieves comparable oncological outcomes with excellent aesthesis relative to traditional ablative procedures for local control. Nipple preservation although not evaluated independently does enhance cosmetic outcomes. *(Preliminary analysis) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-16.

Nipple-sparing mastectomy and immediate breast reconstruction: Critical appraisal of five-year, single-center outcomes.

99 Background: Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom (2:1 ratio of immediate versus delayed respectively). Preservation of the breast envelope, i.e., skin and nipple areola complex (NAC) improves cosmesis. While skin-sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple-sparing mastectomy (NSM) remains controversial. In over 1,800 published NSM cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease-free survival. In our cohort, patient selection criteria included: preoperative lesion characterisation; 5-mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved margins. This study is intended to evaluate the efficacy of loco-regional control in a consecutive cohort of patients, under uniform conditions undergoing nipple-sparing mastectomy and immediate breast reconstruction. We highlight the surgical technique used and propose in/exclusion criteria for appropriate patient selection. Methods: 84 consecutive patients underwent NSM and IBR at Frimley Park Hospital, Surrey, UK (IJL, RD) between January 2004 and December 2008. Data was accrued retrospectively from the institution’s clinical coding, electronic records, and WinPath database. Endpoints recorded include: the incidence of (occult) malignancy at the nipple margins; NAC subcutaneous tissue loss; local (NAC) recurrence rates and disease free survival. Results: The mean age was 51.1 years and follow-up 4.9 years. There was one case of local recurrence in a patient who declined re-excision of close/involved margins. The immediate peri-operative complication rate was within the national mastectomy breast reconstruction audit outcome guidelines. Conclusions: In appropriately selected patients, our findings support nipple preservation at the time of mastectomy and immediate reconstruction as this enhances the cosmetic outcome without compromising oncologic safety.

The Superior Pedicle-Nipple Graft Technique Trumps Medial Pedicle Breast Reduction with Nipple Preservation for Management of Gigantomastia

The Superior Pedicle-Nipple Graft Technique Trumps Medial Pedicle Breast Reduction with Nipple Preservation for Management of Gigantomastia

A Novel Technique for Nipple-Sparing Mastectomy and Immediate Reconstruction in Patients with Macromastia

A Novel Technique for Nipple-Sparing Mastectomy and Immediate Reconstruction in Patients with Macromastia

Prophylactic contralateral surgery: current recommendations and techniques

The use of contralateral prophylactic mastectomy (CPM) from both invasive cancer and ductal carcinoma in situ is increasing in the United States [1], in spite of the fact that only 3% of breast cancer patients in the Surveillance, Epidemiology, and End Results database developed a contralateral cancer at 5 years [2]. Endocrine therapy and trastuzumab, both widely used as adjuvant therapy, reduce the incidence of contralateral cancer by about 50%, suggesting that the risk of contralateral cancer in women treated today is quite low. Most guidelines for prophylactic mastectomy address women at high risk, not women with unilateral cancer. Known or suspected BRCA mutation carriers who develop unilateral cancer have a 40 to 60% risk of developing a contralateral cancer, and CPM is accepted as appropriate therapy in this circumstance. To address the issue of what kind of women undergo CPM, we identified 477 patients who had the procedure at Memorial Sloan-Kettering Cancer Center within 1 year of a unilateral cancer diagnosis and compared them with 2,500 women undergoing unilateral mastectomy in the same period (1997 to 2005). CPM patients were younger (median 46 vs 53 years; P < 0.0001), had smaller tumors (1.2 vs 1.8 cm; P < 0.0001), and were less likely to have positive nodes (47 vs 57%; P < 0.0001). Hormone receptor and HER2 status did not differ between cases and controls. Although 68% of CPM patients reported a family history of breast cancer, only 2% underwent genetic testing. Of these, 34 (7%) were found to have a mutation. The pathology specimens of 6% of patients undergoing CPM were found to contain malignancy (eight invasive, 20 ductal carcinoma in situ). When CPM is performed, it should be done to the same anatomic limit as a therapeutic mastectomy. Skin sparing to facilitate reconstruction is appropriate, but flaps should be the same thickness as is used in a therapeutic mastectomy. The use of nipple sparing is controversial [3]. In order to maintain a blood supply to the nipple areolar complex, some breast tissue must be left behind. Most studies of local recurrence after nipple preservation have been limited to patients with breast cancer, and little is known about its use in the prophylactic setting, particularly regarding risks in BRCA carriers. However, local recurrence is uncommon after nipple sparing for cancer treatment, and improved body image and psychological adjustment after nipple sparing has been reported [3], making this option worthy of consideration in patients undergoing CPM.

Does nipple preservation in mastectomy improve satisfaction with cosmetic results, psychological adjustment, body image and sexuality?

We investigated the influence of nipple areolar complex (NAC) sparing in mastectomy, on patient satisfaction with cosmetic results, body-image, sexuality and psychological well-being. We developed a specific questionnaire and compared two groups of women who underwent radical mastectomy with immediate breast reconstruction (IBR). Between 2004 and 2006, 310 women with NAC preservation and 143 patients with successive NAC reconstruction were mailed the questionnaire at follow-up 1 year after definitive complete breast reconstruction surgery. 256 questionnaires was available. Our results showed significant differences in favour of the NAC sparing group regarding body image (difficulty in looking at themselves naked and being seen naked by their partners after surgery, P = 0.001 and P = 0.003, respectively); regarding satisfaction with the appearance of the nipple (P < .0001) and with the sensitivity of the nipple (P = 0.001); regarding the feeling of mutilation (P = 0.003). NAC sparing in mastectomy has a positive impact on patient satisfaction, body image and psychological adjustment.

Breast conserving surgery with preservation of the nipple-areola complex as a feasible and safe approach in male breast cancer: a case report

IntroductionBreast cancer in men is rare. The evidence about treatment has been derived from data on the management of the disease in women. The usual treatment is for male patients to undergo modified radical mastectomy. There is insufficient experience of breast conserving surgery with preservation of the nipple. The management of patients who demand such an approach for personal reasons remains a challenge for both the surgeon and oncologist.Case presentationA 50-year-old man with a breast cancer was successfully managed with breast conserving surgery with nipple preservation combined with axillary clearance and postoperative radiotherapy, chemotherapy and hormone treatment. Since there are no similar cases in the literature, we discuss the feasibility, safety and possible indications of such an approach.ConclusionDespite the limited indications and evidence about the safety and efficacy of breast conserving surgery with nipple preservation in men with breast cancer, it is a feasible approach if other options are declined by the patient. More studies are necessary to reach firm conclusions about the safety of such an approach.

Subcutaneous mastectomy including conservation of the nipple areolar complex: broadening the indications

Background: Breast conservation therapy has been shown to produce survival rates equivalent to those seen with modified radical mastectomy. Synchronous occult neoplastic involvement of the nipple may lead to incomplete excision of the tumor in patients undergoing breast conservation therapy, possibly leading to recurrence.Study Design: The charts of 803 breast cancer patients treated between 1990 and 1995 at two teaching hospitals were retrospectively reviewed. The patients were divided into three groups: nipple-positive for malignancy (n = 54), nipple-negative for malignancy (n = 404), and nipple-not-removed (n = 345). Ten different clinical and tumor parameters including age, race, primary tumor location, histologic grade, primary tumor size, nodal involvement, TNM stage, estrogen receptor status, DNA ploidy, and S-phase were examined for the ability to predict cancerous nipple involvement.Results: Overall, the rate of nipple positivity was 12%. In univariate analysis pathologic stage, tumor size, lymph node status, histologic grade, and tumor location were significant predictors of positive nipple involvement. Patients with tumors that were stage III or higher were nearly ten times (odds ratio [OR] = 9.8, 95% confidence interval [CI] = 5.5 to 17.7) more likely to have nipple involvement than patients with early-stage tumors. Patients with a tumor size of 4 cm or greater were nearly eight times (OR = 7.8, 95% CI = 4.2 to 14.5) more likely to have nipple involvement than patients with tumor size less than 4 cm. Patients with positive lymph nodes were five times (OR = 5.0, 95% CI = 2.7 to 9.1) more likely to have nipple involvement than patients with negative lymph nodes. Patients with tumors in a central location or that overlapped quadrants were nearly four times (OR = 3.8, 95% CI = 2.2 to 6.8) more likely to have nipple involvement than patients with tumors in other locations. Patients with grade 3 or undifferentiated tumors were three times (OR = 3.0, 95% CI = 1.4 to 6.4) more likely to have nipple involvement than patients with lower grade tumors. In multivariable analysis, stage ≥ 3 (OR = 9.2, 95% CI = 4.2 to 20.3) central/overlap location (OR = 4.1, 95% CI = 2.0 to 8.7) and grade 3 or undifferentiated (OR = 3.1, 95% CI = 1.3 to 7.5) were the only variables that remained significant predictors of nipple involvement.Conclusions: The decision to perform breast conservation surgical procedures with nipple preservation can be difficult, particularly in patients with larger, more centrally located tumors. The multivariable model developed in this study may be useful in predicting the risk of cancerous nipple involvement and selecting appropriate breast conservation patients for nipple preservation.

Oncological considerations of skin-sparing mastectomy

AimTo review evidence concerning the oncological safety of performing skin-sparing mastectomy (SSM) for invasive breast cancer and ductal carcinoma in situ (DCIS). Furthermore, the evidence concerning RT in relation to SSM and the possibility of nipple preservation was considered.MethodsLiterature review facilitated by Medline and PubMed databases.FindingsDespite the lack of randomised controlled trials, SSM has become an accepted procedure in women undergoing mastectomy and immediate reconstruction for early breast cancer. Compared to non-skin-sparing mastectomy (NSSM), SSM seems to be oncologically safe in patients undergoing mastectomy for invasive tumours smaller than 5 cm, multicentric tumours, DCIS or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin in view of the high risk of local recurrence. SSM with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumour is not close to the nipple and a frozen section protocol for the retro-areolar tissue is followed. Although radiotherapy (RT) does not represent a contraindication to SSM, the latter should be used with caution if postoperative RT is likely, since it detracts from the final cosmetic outcome.

Assessment of patients' satisfaction with cosmetic results, impact on body image and sexuality after mastectomy and immediate plastic surgery with nipple preservation

Assessment of patients' satisfaction with cosmetic results, impact on body image and sexuality after mastectomy and immediate plastic surgery with nipple preservation

Nipple preservation during mastectomy.

In a retrospective study of 100 patients with operable breast cancer, microscopic involvement of the nipple-areola complex was found in 16 cases. Each of these 16 cases occurred in patients with centrally situated tumours. In contrast, nipple involvement did not occur with peripherally situated tumours lying greater than 2 cm outside the areolar margin (P less than 10(-6), Fisher's exact test). Nipple involvement was more likely in patients with greater than or equal to 4 positive axillary nodes (P less than 0.01, chi 2 test). From this study it appears that nipple preservation may be undertaken during mastectomy for small peripheral tumours, provided the nipple is clinically normal, and frozen section analysis of the sub-nipple area is shown to be free from tumour invasion. These criteria for nipple preservation were satisfied in 20 patients out of a prospective series of 60. In this group, nipple preservation on the skin flap improved the cosmetic result of breast reconstruction in 35 per cent, and facilitated skin closure in 20 per cent. After a mean follow-up period of 50.4 months, nipple preservation was not associated with any significant excess of local recurrences.

Risk factors for nipple involvement in breast cancer patients

AbstractIntroduction: A clinically normal‐appearing nipple in patients with breast cancer may contain unsuspected neoplastic cells. Preservation of a nipple containing occult malignancy could potentially increase local recurrence rates and affect disease‐free survival. Consequently, patients considered for breast conservation operations with nipple preservation must be carefully selected.Methods: Information available on 382 patients diagnosed and treated with breast cancer at the Clinical Center Nis from 2000 to 2003 were retrospectively reviewed. Multivariate hazard analyses was used to assess the association between potential risk factors of cancerous nipple involvement.Results: The frequency of nipple involvement was 12.04%. Nearly half of the patients had disease stage III and IV. Most patients, 29 (63.04%), had a tumor to nipple distance of less then 2 cm. Twenty‐five patients (54.34%) had more then four positive axillary nodes. A central/overlap tumor location was present in 28 (60.87%) patients. Cox multivariate analysis of prognostic factors showed that Stage III (RH 4.79 (1.50–14.68, 1.50–14.72); P= 0.008), central/overlap tumor location (RH 3.28 (0.90–11.20); P= 0.078) and nuclear grade III or greater (RH 2.26 (0.79 to 6.65); P= 0.065) had a statistically significant effect on malign nipple involvement.Conclusions: The multivariable model used in this study showed a significant association between stage, centrally located tumors and nuclear grade III or greater in predicting the risk of cancerous nipple involvement. Preoperative magnetic resonance imaging or computed tomography scan examinations are recommended for treatment planning of breast cancer, in particular nipple preserving surgery in patients with central/overlap tumor localization and with a tumor to nipple distance of less than 2 cm.

Mastectomy Retaining Nipple as well as Areola

Mr Gordon and his colleagues describe mastectomy with areola preservation (NEAT) in carefully selected cases, and point out the advantage of areola preservation for the patient (April 2001 JRSM, pp. 185-186). However, preservation of the outer nipple can further improve cosmesis without compromising oncological principles. Experience with total duct excision has shown that a demarcation exists between the outer dermo-fibromuscular covering of the nipple and the central duct core. This plane may be utilized to remove the apex of the nipple containing the duct orifices, together with the central duct core, while preserving the outer nipple. This operation, designated ‘core nipple duct excision’, is readily combined with mastectomy. It leaves a diminished (but much appreciated by the patient) nipple in continuity with the areola. The details of the operation and the relevant oncological considerations have been described fully1. Case 3 in Gordon's paper would be eminently suited to this procedure, as would all cases where low-grade cancer is reasonably distanced from the nipple ducts, as required for the NEAT operation.

Parameters that predict nipple involvement in breast cancer

Background: Breast conservation therapy has been shown to produce survival rates equivalent to those seen with modified radical mastectomy. Synchronous occult neoplastic involvement of the nipple may lead to incomplete excision of the tumor in patients undergoing breast conservation therapy, possibly leading to recurrence.Study Design: The charts of 803 breast cancer patients treated between 1990 and 1995 at two teaching hospitals were retrospectively reviewed. The patients were divided into three groups: nipple-positive for malignancy (n = 54), nipple-negative for malignancy (n = 404), and nipple-not-removed (n = 345). Ten different clinical and tumor parameters including age, race, primary tumor location, histologic grade, primary tumor size, nodal involvement, TNM stage, estrogen receptor status, DNA ploidy, and S-phase were examined for the ability to predict cancerous nipple involvement.Results: Overall, the rate of nipple positivity was 12%. In univariate analysis pathologic stage, tumor size, lymph node status, histologic grade, and tumor location were significant predictors of positive nipple involvement. Patients with tumors that were stage III or higher were nearly ten times (odds ratio [OR] = 9.8, 95% confidence interval [CI] = 5.5 to 17.7) more likely to have nipple involvement than patients with early-stage tumors. Patients with a tumor size of 4 cm or greater were nearly eight times (OR = 7.8, 95% CI = 4.2 to 14.5) more likely to have nipple involvement than patients with tumor size less than 4 cm. Patients with positive lymph nodes were five times (OR = 5.0, 95% CI = 2.7 to 9.1) more likely to have nipple involvement than patients with negative lymph nodes. Patients with tumors in a central location or that overlapped quadrants were nearly four times (OR = 3.8, 95% CI = 2.2 to 6.8) more likely to have nipple involvement than patients with tumors in other locations. Patients with grade 3 or undifferentiated tumors were three times (OR = 3.0, 95% CI = 1.4 to 6.4) more likely to have nipple involvement than patients with lower grade tumors. In multivariable analysis, stage ≥ 3 (OR = 9.2, 95% CI = 4.2 to 20.3) central/overlap location (OR = 4.1, 95% CI = 2.0 to 8.7) and grade 3 or undifferentiated (OR = 3.1, 95% CI = 1.3 to 7.5) were the only variables that remained significant predictors of nipple involvement.Conclusions: The decision to perform breast conservation surgical procedures with nipple preservation can be difficult, particularly in patients with larger, more centrally located tumors. The multivariable model developed in this study may be useful in predicting the risk of cancerous nipple involvement and selecting appropriate breast conservation patients for nipple preservation.