The Use of Neoadjuvant Systemic Therapy to Facilitate Nipple-sparing Mastectomy and Immediate Reconstruction

Abstract

Background:

Neoadjuvant systemic therapy (NST) is a well-established strategy to convert patients initially requiring a mastectomy to breast-conserving surgery, but has not been studied for its efficacy in facilitating total skin-sparing mastectomy (TSSM) and reconstruction in patients with tumors that encroach on the skin- and/or nipple–areola complex (NAC).

Methods:

The author reviewed his experience from August 2010 through July 2024 with the use of NST to facilitate TSSM and the immediate implant-based reconstruction in patients who were initially not candidates for this approach because of tumor encroachment on the NAC and/or skin envelope.

Results:

Between 2010 and 2024, the author identified 1425 patients who underwent TSSM with immediate implant reconstructions in his surgical practice. Of these, 160 patients initially presented with disease that precluded preservation of the skin and/or NAC and underwent NST, allowing for TSSM and immediate reconstruction in 138 (86.3%) patients.

Conclusions:

The use of NST in patients with tumors that encroach on the NAC and/or skin envelope can be used to facilitate TSSM and reconstruction in patients who otherwise would not be candidates for this approach. Reconstructive surgeons should familiarize themselves with the principles of and indications for NST and play an active role in the multidisciplinary treatment planning of these complex patients.

Takeaways

Question: How can we convert patients who are not candidates for skin- or nipple-sparing procedures secondary to their cancer burden to more conservative mastectomy surgery?

Findings: This study demonstrates that the use of appropriate neoadjuvant systemic therapy can facilitate successful performance of skin- and nipple-sparing mastectomy surgery in patients who would not have been initially offered this option.

Meaning: Neoadjuvant therapy should be considered in all patients with large tumor burdens who are initially not candidates for a conservative mastectomy to help conserve the nipple and/or skin envelope to facilitate skin- or nipple-sparing mastectomy and immediate reconstruction.

INTRODUCTION

The use of neoadjuvant chemotherapy (NACT) or neoadjuvant endocrine therapy (NET) to facilitate breast-conserving surgery (BCS) is a well-established modality in breast surgical oncology.¹ This allows surgeons to downsize larger breast cancers to more favorable tumor-to-breast size ratios, allowing for BCS in patients who were initially candidates only for mastectomy. In some cases, neoadjuvant systemic therapy (NST) is used to convert inoperable, locally advanced tumors to operable ones.² We reasoned that NST could also have an indication to downsize breast cancers in close proximity to the skin and/or nipple–areola complex (NAC) to allow for total skin-sparing mastectomy (TSSM) and immediate reconstruction. Patients with cancers in close proximity to their skin envelopes and/or NACs typically require excision of these structures, compromising the quality of the reconstruction and/or making immediate reconstruction impossible, or mandating the use of a tissue expander.³ Successful conversion of these patients to a more conservative mastectomy can have profound effects on the final aesthetics of reconstruction, the ability to offer immediate and/or direct-to-implant reconstruction (DTIR), and long-term patient satisfaction.⁴

The use of NACT is standard in patients with stage 2 or node-positive triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2/neu)–positive breast cancers.⁵ Oncological considerations here dictate the sequence of treatment with definitive surgery following the completion of systemic therapy. Many of these patients present with tumors that encroach upon the skin and/or nipple but will have excellent responses to chemotherapy, allowing for conservative mastectomy and reconstruction.^6–12 The safety of nipple-sparing mastectomy has been established in these cancers after completion of NACT, provided posttreatment imaging suggests resolution of disease and absence of skin or NAC involvement,¹² and their final pathology demonstrates clear surgical margins.^6,7,10 For patients with larger (1–2 cm) stage 1 TNBC or HER2/neu–positive breast cancer, the American Society for Clinical Oncology and the St. Gallen Guidelines leave the use of NACT to the discretion of the multidisciplinary team.^13,14 For these patients, who are motivated to proceed with TSSM, we have taken an active role in requesting that our medical oncologists administer NACT if the tumor is in close proximity to the NAC and/or skin envelope, making TSSM difficult.

Although the standard of care dictates the use of NACT for stage 2 TNBC or HER2/neu–positive breast cancer and it can be considered for stage 1 TNBC and HER2/neu–positive cancers,^12,13 there are no clear guidelines for administering NACT for estrogen receptor–positive (ER+), HER2/neu–negative breast cancers unless there is evidence of locally advanced disease or significant lymph node involvement.¹⁴ Patients with these tumors often undergo surgery first followed by genomic analysis of their cancers to determine whether there is any benefit to adjuvant chemotherapy.¹⁵ These ER+ breast cancers can have a wide range of chemosensitivities, ranging from those comparable to TNBCs to those that are chemoresistant and will only respond to endocrine therapy. Genomic analysis has revolutionized decision-making for these ER+, HER2/neu–negative breast cancers, accurately predicting which patients benefit from adjuvant chemotherapy.¹⁶

There is a growing body of literature that supports the use of genomic profiling to determine the benefit of NST for ER+, HER2/neu–negative cancers in the preoperative setting, instead of waiting for final surgical pathology.^17–20 In the past, genomic profiling was performed after surgery for these tumors. Genomic profiling in the preoperative setting can help surgeons determine which patients will benefit from NACT or NET to downsize tumors, facilitate breast conservation, and/or reduce the morbidity of axillary surgery for patients who have known metastatic spread to the axillary lymph nodes.²¹ We reasoned that we could also use genomic analysis to determine which ER+, HER2/neu–negative breast cancers would respond to NACT or NET in the preoperative setting to facilitate TSSM and immediate reconstruction in patients who were initially not candidates for this based on tumor encroachment on the skin and/or the nipple. This was often motivated by patients who were adamant about obtaining the best possible aesthetic result. In some cases, genomic profiling revealed a benefit from chemotherapy, and these patients were referred to medical oncology for NACT. Other patients, who were determined to have no benefit from chemotherapy, underwent 4–6 months of NET. This report described our experience using NACT or NET to convert patients who were not initially candidates for skin- or nipple-sparing procedures to TSSM with immediate implant-based reconstruction. In some cases, NST recommendations were dictated by oncologists given the size of the tumor, lymph node status, or molecular subtype (TNBC and HER2/neu–positive cancer). In other cases, neoadjuvant options were indicated by the author, in collaboration with the medical oncologist and taking genomic profiling results into consideration, to downsize tumors where the need for NST was optional (could be given in either the neoadjuvant or adjuvant settings).

METHODS

The author retrospectively reviewed all TSSM and immediate reconstructions he performed at a single institution between August 2010 and July 2024 using a prospectively maintained database. The author collected the following data: initial and posttreatment tumor size, initial stage, hormone receptor status (estrogen and progesterone), HER2/neu status, closest initial distance of tumor to NAC and/or anterior skin margin, final margin status and pathological distance to NAC or anterior skin margin, type of NST (NACT versus NET), length of follow-up, incidence of local and/or distant recurrence, major surgical complications requiring reoperation, incidence of reconstructive failure, and incidence of attempted TSSM with positive margins requiring re-excision or conversion to skin-sparing mastectomy. Our analysis only included data from the breast diagnosed with cancer and did not include data from any prophylactic or contralateral surgery.

Patients were eligible for TSSM if they did not present with bloody nipple discharge, Paget disease, or inflammatory breast cancer. Nipple or skin invasion on clinical examination or preoperative imaging did not exclude patients from TSSM if this resolved on posttreatment clinical examination and imaging. All patients met with a medical oncologist who approved the neoadjuvant approach. All patients were imaged with diagnostic mammography, ultrasound, and magnetic resonance imaging before and after NST to assess response. Patients were seen periodically by the author while they were receiving NST to ensure they were responding to therapy. We proceeded with surgery 4–6 weeks after NACT was completed but did not delay surgery after NET.

We routinely used inframammary fold or lateral radial “lazy S” incisions, and nipple-sparing Wise-pattern skin-reducing incisions. Patients with close margins (<1 mm) or positive margins were advised to undergo re-excision or radiotherapy. In the event that a close or positive margin was beneath the NAC, nipple or NAC resection was the standard, but re-excision was more routinely considered later in our experience. Although the author initially exclusively performed subpectoral tissue expander reconstructions with the acellular dermal matrix, he transitioned, almost exclusively, to a prepectoral approach using either a tissue expander or definitive implant with or without the use of an absorbable, biosynthetic mesh. Statistical analyses were performed using IBM SPSS, version 30.0 (IBM Corp., Armonk, NY).

For tumors demonstrating a complete pathological or imaging response, the final distance to the skin recorded was arbitrarily given a value of 1 cm. For patients whose final pathology was clear but had reconstructive failure, we counted this as a successful TSSM (the overwhelming majority of these patients were eventually reconstructed).

RESULTS

Between August 2010 and July 2024, the author identified 1426 women with breast cancer who were considered for TSSM and reconstruction. The demographics and oncological characteristics of this patient cohort are presented in Table 1. Of these, 978 (68.6%) patients received chemotherapy, of whom 449 (44.9%) and 529 (54.1%) received neoadjuvant and adjuvant chemotherapy, respectively. Thirty-five (4.2%) women received NET before TSSM. Of the 1426 women who were considered for TSSM and immediate reconstruction, 1340 (94.0%) were successful. Of the 484 women who underwent NACT or NET and were considered for TSSM and reconstruction, 445 (91.9%) were successful.

Table 1.

All Patients Between 2010 and 2024 Undergoing NSM and Reconstruction: Demographics, Comorbidities, and Oncological Characteristics

	Patients(N = 1426)
Age, y	52.6 (±5.9)
BMI, kg/m2	28.6 (±5.7)
Hypertension, n (%)	595 (41.7)
Diabetes, n (%)	205(14.4)
Prior XRT, n (%)	75 (5.3)
Molecular subtype, n (%)
HER2/neu+	257 (18.0)
ER+, HER2/neu−	964 (67.6)
TNBC	205 (14.4)
Oncological treatment, n (%)
Chemotherapy	978 (68.6)
Neoadjuvant	449 (44.9)
Adjuvant	529 (54.1)
Neoadjuvant endocrine	35 (4.2)
Adjuvant endocrine	413 (29.0)

NSM, nipple-sparing mastectomy; XRT, radiotherapy.

Of these 484 women who underwent neoadjuvant treatment before mastectomy, 160 (33.0%) had pretreatment imaging demonstrating tumor-to-skin or NAC distances of less than 2 mm and were considered questionable candidates for TSSM (Table 2, Figs. 1–3). (See figure, Supplemental Digital Content 1, which displays a pretreatment photograph of a 44-year-old woman with a 1.1-cm TNBC who desired bilateral mastectomy and DTIR. She had retraction of her inferior pole right breast skin that would make this procedure difficult, https://links.lww.com/PRSGO/E767.) (See figure, Supplemental Digital Content 2, which demonstrates how the patient required chemotherapy, but the standard of care allowed for either a neoadjuvant or adjuvant approach. We were able to facilitate a nipple-sparing, direct-to-implant approach and optimize her aesthetic outcome by requesting that her chemotherapy be given before surgery, https://links.lww.com/PRSGO/E768.) (See figure, Supplemental Digital Content 3, which displays a 39-year-old woman with a 4.5-cm ER−, Her2/neu–positive right breast cancer invading the skin and NAC. NACT was recommended by medical oncology, https://links.lww.com/PRSGO/E769.) (See figure, Supplemental Digital Content 4, which displays a patient 6 mo after the completion of radiotherapy and bilateral nipple-sparing mastectomy with DTIR. Her final pathology demonstrated a complete pathological response, allowing for a TSSM with immediate reconstruction, https://links.lww.com/PRSGO/E770.) Demographics and oncological characteristics of this group are presented in Table 2. After completing systemic therapy, 138 (86.2%) of these questionable candidates successfully underwent TSSM with immediate reconstruction. The remaining 22 (13.8%) patients were either not offered TSSM and reconstruction because posttreatment imaging revealed either progression of disease or minimal effect, or required their NACs and/or significant segments of their skin envelopes excised to obtain clear margins. Although most HER2/neu–positive breast cancers were successfully converted to TSSM and reconstruction (92%), this strategy was less successful in ER+, HER2/neu–negative patients undergoing NACT (74%) (Table 2). After systemic therapy, the average tumor size decreased from 3.1 ± 1.2 to 1.3 ± 0.8 cm (P = 0.001), and the distance between the breast cancer and NAC or skin envelope significantly increased from 0.13 ± 0.05 to 0.55 ± 0.17 cm (P = 0.02) (Table 2). Of the 160 patients who received NACT or NET and were initially not candidates for TSSM, the molecular subtypes were the following: TNBC, 36 (22.5%); HER2/neu -positive breast cancer, 71 (44.3%); and ER+, HER2/neu -negative breast cancer, 53 (33.1%) (Table 2). All 15 patients receiving NET in this group had ER+, HER2/neu–negative breast cancers. All patients, regardless of cancer molecular subtype, who were initially not considered good candidates for TSSM and reconstruction, experienced a statistically significant reduction in tumor size and an increase in the distance to the closest margin (skin or NAC) after NST (Table 2).

Table 2.

Patient Cohort, Initially Not Candidates for Total Skin-Sparing Mastectomy, Undergoing Neoadjuvant Therapy: Demographics, Oncological Variables Before and After Treatment

	Patients (n = 160)	Successful NSM, n (%)	PreRx Size, cm		PostRx Size, cm	P	Distance to Skin/NAC PreRx, cm	Distance to Skin/NAC PostRx, cm	P
Age, y	48.6 (±4.9)
BMI, kg/m2	26.6 (±4.7)
Hypertension	18 (11.3%)
Diabetes	15 (9.4%)
Prior XRT	9 (5.6%)
All patients	160	138 (86)	3.1 (± 1.2)	1.3 (± 0.8)		0.004	0.13 (± 0.05)	0.55 (± 0.17)	0.02
HER2/neu	71	65 (92)	2.9 (± 0.6)	0.8 (± 0.6)		0.001	0.10 (± 0.03)	0.86 (± 0.27)	0.003
ER+, HER2/neu−NACT	38	28 (74)	3.9 (± 0.8)	2.7 (± 0.6)		0.03	0.13 (± 0.05)	0.36 (± 0.37)	0.04
ER+/HER2/neu−NET	15	13 (87)	4.4 (± 1.2)	2.4 (± 1.6)		0.01	0.12 (± 0.3	0.33 (± 0.21)	0.01
TNBC	36	32 (89)	3.5 (± 0.8)	1.0 (± 0.5)		0.00	0.15 (± 0.04)	0.91 (± 0.4)	0.006

NSM, nipple-sparing mastectomy; PostRx, posttreatment; PreRx, pretreatment; XRT, radiotherapy.

Fig. 1.

A 61-year-old woman with an extensive ER+, HER2/neu–negative, node-negative right breast cancer encroaching upon the nipple and skin envelope. The patient desired nipple-sparing mastectomy and immediate reconstruction. Genomic testing revealed the tumor to be chemosensitive, and the patient was referred to medical oncology for NACT. Preoperative views of the anterior (A) and lateral right breast (B) of the patient, with locally advanced breast cancer seen encroaching on the skin envelope.

Fig. 3.

A patient who underwent bilateral TSSM, left bipedicle adipodermal mastopexy, and DTIR, shown 6 months after completion of postmastectomy radiotherapy. Final pathology revealed 5 mm of residual disease with clear margins. Without the neoadjuvant approach, the patient would have required excision of her nipple and a large portion of her skin envelope, tissue expander placement with multiple office visits for expander filling, and additional surgery for implant exchange and nipple reconstruction.

Fig. 2.

Magnetic resonance imaging of the patient in Figure 1. Pretreatment (A) and posttreatment (B) dynamic contrast-enhanced breast magnetic resonance imaging demonstrating T1-weighted transaxial maximum intensity projection and subtraction images using a 3-dimensional gradient-echo sequence with diffusion-weighted imaging. Imaging reveals an initially extensive cancer concerning for both skin and nipple involvement. After completion of NACT, posttreatment imaging reveals a complete response with no obvious skin and/or nipple involvement, allowing us to proceed with TSSM and immediate reconstruction.

For patients with TNBCs undergoing NACT, 25 (69.4%) had at least stage 2 breast cancer (primary tumor >2 cm and/or node positive) (Table 3). These patients were all recommended to undergo NACT after a medical oncology consultation. After chemotherapy, the average tumor size decreased from 3.5 ± 0.8 to 1.0 ± 0.5 cm (P = 0.003), and the distance between the breast cancer and NAC or skin envelope significantly increased from 1.5 ± 0.04 to 9.1 ± 3.7 mm (P = 0.004) (Table 2). Eleven (30.6%) patients had stage 1 breast cancer, and for 9 (82%) of these patients, the neoadjuvant approach was coordinated after discussion between the author and the treating medical oncologist and multidisciplinary tumor board (as the neoadjuvant approach in stage 1 TNBCs is up to the discretion of the multidisciplinary team) (Table 3). Of the 36 patients who were initially not candidates for TSSM and reconstruction, 32 (88.9%) were converted to successful candidates (Table 2).

Table 3.

Breast Cancer Staging for the Neoadjuvant Cohort Not Initially Candidates for NSM and Reconstruction and Recommendations for NST

	Reconstructive Approach
	Patients (n = 160)	Stage 1	Stage 2	Stage 3	Medical Oncology Recommendation, n (%)	Motivated by Surgeon (With MDT and Medical Oncology Approval), n (%)
All patients
HER2/neu+	71	19	40	12	56 (79)	15 (21)
ER+, HER2/neu−NACT	38	2	9	27	15 (40)	23 (60)
ER+/HER2/neu−NET	15	1	6	8	2 (13)	13 (87)
TNBC	6	11	19	6	27 (75)	9 (25)

MDT, multidisciplinary team; NET, neoadjuvant endocrine therapy; NSM, nipple-sparing mastectomy.

For patients with HER2/neu–positive breast cancer undergoing NACT, 52 (73.2%) had at least stage 2 breast cancer (primary tumor greater than 2 cm or node positive) (Table 3). These patients were all recommended to undergo NACT after medical oncology consultation. After chemotherapy, the average tumor size decreased from 2.9 ± 0.6 to 0.8 ± 0.6 cm (P = 0.008), and the distance between the breast cancer and NAC or skin envelope significantly increased from 1.0 ± 0.3 to 8.6 ± 2.7 mm (P = 0.009) (Table 2). Nineteen (17.1%) patients had stage 1 breast cancer, and for 15 (79%) of these patients, the neoadjuvant approach was coordinated after discussion among the author, the treating medical oncologist, and the multi-disciplinary team (as the neoadjuvant approach for stage 1 HERr2/neu–positive breast cancers is up to the discretion of the multidisciplinary team) (Table 3). Of the 71 patients who were initially not candidates for TSSM and reconstruction, 65 (91.5%) were converted to successful candidates (Table 2).

For patients with ER+/HER2/neu–negative breast cancers who received NACT, 2 (5.2%) patients had stage 1 breast disease, 9 (23.4%) presented with stage 2 disease, and 27 (71.1%) presented with stage 3 disease (defined as primary tumors >5 cm with positive lymph nodes or tumors <5 cm with fixed or matted nodes or involvement of the internal mammary lymph nodes) (Table 3). For stage 1 and stage 2 breast disease, the decision to proceed with NACT in these patients was often determined by genomic testing performed by the author on the core biopsy specimen, which revealed if the tumor was chemosensitive. Tumors determined to be chemoresistant underwent NET. For 23 (60%) patients, the neoadjuvant approach was coordinated by the author after genomic analysis of the tumor and discussion with the medical oncologist and multi-disciplinary team (Table 3). After chemotherapy, the average tumor size in this group of patients decreased from 3.9 ± 0.8 to 2.7 ± 0.6 cm (P = 0.004), and the distance between the breast cancer and NAC or skin envelope significantly increased from 1.3 ± 0.5 to 4.6. ± 3.7 mm (P = 0.006) (Table 2). Of the 38 patients who were initially not candidates for TSSM and reconstruction and received NACT, 28 (73.7%) were converted to successful candidates (Table 2).

For patients with ER+/HER2/neu–negative breast cancers who received NET, 1 (7%), 6 (40%), and 8 (53%) patients presented with stage 1, 2, and 3 disease, respectively (Table 3). The decision to proceed with NET was made by the author in 13 (87%) patients after discussion with the medical oncologist and multidisciplinary team and was guided by the results of tumor genomic testing that predicted sensitivity to antihormonal therapy or by other routine pathological results (grade, Ki67, degree of estrogen and progesterone receptor positivity, etc.). After 4–6 months of NET, the average tumor size in this group of patients decreased from 4.4 ± 1.2 to 2.4 ± 1.6 cm (P = 0.002), and the distance between the breast cancer and NAC or skin envelope significantly increased from 1.2 ± 0.3 to 3.3 ± 2.1 mm (P = 0.004) (Table 2). Of the 15 patients who were initially not candidates for TSSM and reconstruction and received NET, 13 (86.7%) were converted to successful candidates.

The rate of major surgical complications (requiring operative intervention, inpatient admission, or intravenous therapy) is shown in Table 4. We compared the rates of these complications between patients who were considered good and poor candidates for TSSM and reconstruction but who also received NST. There are no significant differences in the rates of major complications between patients who were considered good or poor candidates for TSSM and reconstruction after receiving NST (Table 4).

Table 4.

Comparison of Major Complications Rates Between Patients Who Were and Were Not Good Candidates for NSM and Reconstruction Before NST

	All Patients (N = 484)	Good Candidates (n = 324)	Poor Candidates (n = 160)	P
All major, n (%)	58 (12)	35 (10.8)	23 (14.4)	0.67
Hematoma, n (%)	8 (1.7)	6 (1.9)	2 (1.3)	0.26
Seroma, n (%)	12 (2.5)	9 (2.8)	3 (1.9)	0.55
Infection, n (%)	17 (3.5)	12 (3.7)	5 (3.1)	0.75
Postoperative wound dehiscence/tissue necrosis, n (%)	20 (3.9)	14 (4.3)	6 (3.8)	0.77
Reconstructive failure, n (%)	44 (9.1)	26 (8.0)	18 (11.1)	0.25
Local recurrence, n (%)	27 (5.6)	20 (6.2)	7 (4.4)	0.42
Time to local recurrence, y	6.3	7.7	5.3	0.11
Distant recurrence, n (%)	44 (9.1)	31 (9.6)	13 (8.1)	0.60
Time to distant recurrence, y	3.8	5.1	4.0	0.17

NSM, nipple-sparing mastectomy.

The median follow-up period for all patients who were not initially candidates for TSSM and reconstruction was 69 months (6 –118 mo). For the 22 (14%) patients who did not successfully undergo TSSM (of the initially 160 who were deemed poor candidates before NST), 15 (68%) patients demonstrated minimal improvement on posttreatment imaging or concerning physical examination findings, and TSSM was not attempted. The remaining 7 (32%) patients demonstrated improvement on posttreatment imaging and acceptable physical examination findings, but final surgical pathology revealed involved margins, necessitating nipple and/or significant skin resection.

The rate of local recurrence was not significantly different between patients who were (20 [6.2%]) and were not (7 [4.4%]) thought to be good candidates for TSSM before NST (P = 0.42). Similarly, the rate of distant recurrence was not significantly different between patients who were (31 [9.6%]) and were not (13 [8.1%]) initially thought to be good candidates for TSSM before NST (P = 0.60) (Table 5) . Although the use of NST had a statistically significant impact on final tumor size and margins in patients who were either good or poor candidates for TSSM and reconstruction before starting systemic treatment, the group that was thought to be good candidates before administration of systemic therapy had a higher likelihood of successful TSSM and reconstruction (94.1% versus 86.2%, P = 0.035).

Table 5.

Oncological Outcomes for the Total Patient Cohort, Neoadjuvant Cohort, and Both Good and Poor Candidates for NSM

	Total Patient Cohort (N = 1426)	NST Cohort (n = 484)	Good Candidates (n = 324)	Poor Candidates (n = 160)
Complete response, n (%)	369 (26)	218 (45)	150 (46)	68 (43)
Partial response, n (%)	925 (65)	210 (43)	142 (44)	75 (47)
Progression of disease, n (%)		56 (12)	32 (10)	17 (11)
Progression of disease preventing NSM, n (%)		48 (10)	25 (8)	15 (9)
Close or positive margins, n (%)		27 (6)	18 (6)	9 (6)
Close or positive margins preventing NSM, n (%)		21 (4)	14 (4)	7 (4)
Requirement for RT, n (%)	428 (30)	218 (45)	133 (41)	85 (53)

NSM, nipple-sparing mastectomy; RT, radiotherapy.

DISCUSSION

The use of NACT or NET to facilitate BCS is a well-established modality in breast surgical oncology.¹ This allows surgeons to downsize larger breast cancers to more favorable tumor-to-breast size ratios, allowing for BCS in patients who were initially only candidates for mastectomy. We propose that the same rationale could be used to facilitate TSSM and reconstruction in patients who were not candidates due to tumor encroachment on the skin and/or NAC. If one considers the skin and/or nipple as just an anterior margin rather than simply an anatomical boundary, as many surgeons have proposed,^22–24 this strategy is intuitively logical. The use of NST is known to reduce the risk of positive margins for patients undergoing BCS,²⁵ and in mastectomy patients, it reduces the risk of anterior margin involvement, the most important margin assessed for patients undergoing TSSM. In this case, the tumor is downsized not to preserve breast tissue and conserve the breast, but instead to conserve the skin envelope and facilitate TSSM and reconstruction.

For patients with triple-negative or HER2/neu–positive breast cancers that are greater than 2 cm or node-positive, the decision to proceed with NACT is the standard and dictated by our medical oncologists.^5,12,13 Reconstructive surgeons should be aware that many of these cancers will have robust responses to chemotherapy, and patients who were initially not candidates for TSSM and immediate reconstruction will be able to have safe preservation of their skin and/or NAC.^6–11 With chemotherapy and immunotherapy, approximately 65% of patients with TNBCs will have a complete pathological response, and many of whom have just partial responses will still be able to proceed with TSSM.¹² TSSM and reconstruction have been proven to be safe in these patients who have excellent responses to chemotherapy.²⁶ ER− and HER2/neu–positive cancers will have an even a greater likelihood of a complete pathological response, nearly 80%, again facilitating TSSM and reconstruction, and those with a good partial response often still proceed with a conservative mastectomy.⁵ Patients with ER+, HER2/neu–positive breast cancers have the lowest rate of a complete pathological response in these patients, nearly 50%, but many more with just partial responses will still be excellent candidates for TSSM and immediate reconstruction.

The decision to give NACT for triple-negative or HER2/neu breast cancers measuring between 1 and 2 cm is often debated and left up to the discretion of the medical oncologist.^12,13 For patients who are motivated to conserve their nipples and proceed with TSSM with tumors in close proximity to their NAC making preservation challenging or unsafe, reconstructive surgeons should be aware of this and discuss NACT with the patient and medical oncologists. In the author’s experience, medical oncologists are often indifferent on whether these patients proceed with a neoadjuvant or adjuvant approach and are usually willing to give chemotherapy upfront if requested by the patient or reconstructive surgeon.

Unlike TNBCs or HER2/neu–positive breast cancers, the decision to proceed with NACT for patients who are ER+ and HER2/neu–negative is more complex.¹⁴ These patients are usually only given upfront chemotherapy if they present with locally advanced breast cancers and/or multiple positive lymph nodes. For patients with less extensive cancers, chemotherapy is often decided on after surgical resection by assessing the genetics of their breast cancer, which predicts risk of recurrence and benefit from chemotherapy.^15,16 Recent studies have also looked at genetic assessment of these cancers in the preoperative setting to determine their chemosensitivity and decide on an NET or NACT approach.^17–21 Low-risk cancers receive 4–6 months of NET, whereas high-risk cancers are referred to medical oncology for a standard course of NACT. This strategy is most commonly used to downsize larger cancers to facilitate BCS, but we have adopted this approach in patients with extensive cancers that encroach upon the skin and/or nipple who want TSSM to conserve the NAC and skin envelope. The vast majority of these patients will have enough of a response (very few of them will have complete responses) to convert them from poor candidates for TSSM and immediate reconstruction to good candidates for this approach.

This study was performed by a surgeon who performs both surgical oncology and reconstructive surgery, which is unusual and may be difficult to extend to other practice settings. It should also be noted that the indications for NST are constantly changing, and while the principles described here are currently valid, they are not immutable, and reconstructive surgeons would be encouraged to keep themselves constantly updated on changes in recommendations for NST.

CONCLUSIONS

Although the use of NST is a well-established strategy to facilitate BCS in patients with larger breast cancers, we demonstrate here that it can also be used to convert patients with cancers that encroach upon the NAC and/or skin envelope into good candidates for TSSM and immediate reconstruction. NST is known to reduce the risk of positive margins in patients undergoing BCS²⁵ and, by extension, facilitates a clear anterior margin (skin and/or NAC) in patients undergoing TSSM. We encourage all reconstructive breast surgeons to familiarize themselves with the basic principles of NST. This will allow reconstructive surgeons to advocate for their patients who are motivated to proceed with TSSM and meaningfully contribute to the multidisciplinary care of these complex patients.

DISCLOSURE

The author has no financial interest to declare in relation to the content of this article.