Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Triple-negative breast cancer (TNBC):
  • Is a term that has historically been applied to cancers that:
    • Lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
• TNBC:
  • Tends to behave more aggressively than other types of breast cancer
• Unlike other breast cancer subtypes (ie, ER-positive, HER2-positive subtypes):
  • There are no approved targeted treatments available:
    • Although immunotherapy (in combination with chemotherapy) is available for those with advanced TNBC:
      • That expresses programmed cell death ligand 1 (PD-L1)
  • One definition “triple-negative” to mean cancers that have:
    • Less than 1% expression of ER and PR as determined by immunohistochemistry (IHC), and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not amplified), according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
  • Although the basic principles of diagnosis and management of TNBC are similar to those of breast cancer in general:
    • Many aspects, including risk factors, molecular and pathologic characteristics, natural history, and chemotherapy sensitivity, are unique to TNBC

• USPSTF Issues Draft Recommendation Statement on Screening for Breast Cancer: All Women Should Be Screened Every Other Year, Beginning at Age 40
• Today, the U.S. Preventive Services Task Force (USPSTF) posted a draft recommendation statement on screening for breast cancer.
• The USPSTF now recommends that all women get screened for breast cancer every other year starting at age 40 years.
• More research is needed on whether or not women with dense breasts should have additional screening with breast ultrasound or magnetic resonance imaging and on the benefits and harms of screening in women older than 75 years

• National Comprehensive Cancer Network (NCCN) guidelines:
  • Recommend surgical management for local control:
    • For women with early stage invasive breast cancer
• Several studies have shown an equivalence in overall and / or breast cancer-specific survival rates:
  • For breast conservation with radiation compared to mastectomy among early stage breast cancer patients
• For patients with ER+ disease:
  • Endocrine therapy with tamoxifen or aromatase inhibitors is prescribed after surgery
• A systematic review evaluated the efficacy of primary endocrine therapy alone versus surgery in women over 70 years old with operable tumors:
  • The review reported similar survival between the two groups:
    • But women treated with surgery had lower rates of local failure when compared to endocrine therapy alone:
      • The authors concluded that primary endocrine therapy should be reserved for women who are unfit for surgery or decline surgery
• Sentinel node biopsy has become the standard method for staging the axilla in women with early stage breast cancer:
  • Who are clinically node negative
• Axillary dissection:
  • Is only performed in women with documented nodal involvement, inflammatory breast cancers, or those who fail lymphatic mapping
• References
  • National Comprehensive Cancer Network. Breast Cancer. 2023; https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
  • Fisher B, Anderson S, Bryant J, et al. Twenty-year followup of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. New Engl J Med. 2002;347(16):1233-1241.
  • Litiere S, Werutsky G, Fentiman IS, et al. Breast-conserving therapy versus mastectomy for stage I-II breast cancer: 20 year followup of the EORTC 10801 phase 3 randomized trial. Lancet Oncol. 2012;13(4):412-419.
  • Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. New Engl J Med. 2002;347(16):1227-1232.
  • Morgan J, Wyld L, Collins KA, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database Syst Rev. 2014(5). https://www.cochrane.org/CD004272/BREASTCA_surgery-versus-primary-endocrine-therapy-for-elderly-women-with-operable-primary-breast-cancer Accessed August 25, 2019.

• The second generation of laryngeal preservation trials were published in 2003
• The RTOG 91–11 trials:
  • Showed that both concomitant and neo-adjuvant chemoradiotherapy with cisplatin:
    • Resulted in no statistically significant differences in survival compared to radiotherapy alone:
      • However, laryngeal preservation was highest with concomitant chemoradiotherapy (84%) compared to neo-adjuvant chemoradiotherapy (72%) and radiotherapy alone (67%)
    • On the other hand, concomitant chemoradiotherapy resulted in significantly worse acute toxicity compared to induction and chemotherapy and radiotherapy alone
• Reference:
  • Forastiere AA, Goepfert H, Maor M et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. New England Journal of Medicine 2003; 349: 2091–8.

• Pathologic nipple discharge:
  • Is characteristically spontaneous, unilateral, uni-ductal or bloody
• Physiologic discharge:
  • Is nonspontaneous, bilateral, and milky
• The most common causes for pathologic nipple discharge are:
  • Benign:
    • Intraductal papillomas
    • Duct ectasia
• In a patient with a pathologic nipple discharge:
  • And the presence of abnormal clinical findings on imaging or physical exam:
    • Is associated with increased risk of malignancy:
      • 38% vs. 2%
• Contemporary workup for nipple discharge includes:
  • Mammography
  • Evaluation of the retroareolar region with ultrasound
    • Patients with normal findings on mammography, ultrasound, and physical exam:
      • Can be further evaluated with breast MRI, as it is highly sensitive and specific for cancer
• A patient with abnormalities in the physical exam and in imaging (ultrasound or mammography:
  • Would need surgical intervention even with a negative breast MRI
• Surgical management of nipple discharge includes:
  • Excision of a single duct or central duct apparatus:
    • Depending on the number of ducts involved
• References
• Li GZ, Wong SM, Lester S, Nakhlis F. Evaluating the risk of underlying malignancy in patients with pathologic nipple discharge. Breast J. 2018;24(4):624-627.
• de Paula IB, Campos AM. Breast imaging in patients with nipple discharge. Radiol. Bras. 2017;50(6):383-388.
• Yilmaz R, Bender O, Celik Yabul F, Dursun M, Tunaci M, Acunas G. Diagnosis of nipple discharge: value of magnetic resonance imaging and ultrasonography in comparison with ductoscopy. Balkan Med J. 2017;34(2):119-126.

• Current consensus guidelines from the American Society of Breast Surgeons:
  • Do not recommend contra lateral prophylactic mastectomy (CPM):
    • For women with sporadic breast cancers
• A Cochrane review of eight studies evaluating patients who underwent CPM concluded that:
  • While CPM reduces risk of contralateral breast cancer:
    • It is not associated with improved survival
• Reasons for not recommending CPM include:
  • A low estimated risk of cancer in the contralateral breast:
    • 2% to 6% over 10 years
  • Increased complication rates
  • Studies showing that CPM does not improve survival or recurrence from the index cancer

References

Lostumbo L, Carbine N, Wallace J, Ko H. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst Rev 2004(4):CD002748.

Boughey JC, Attai DJ, Chen SL, et al. Contralateral prophylactic mastectomy consensus statement from the american society of breast surgeons: additional considerations and a framework for shared decision making. Ann Surg Oncol. 2016;23(10):3106-3111.

• Currently, wire localization (WL):
  • Is the most commonly used technique for guiding excision of nonpalpable lesions in the breast:
    • It may also be used to localize a clipped axillary node
• However, WL may require coordination of scheduling in the operating room and radiology, result in patient discomfort, and the wire may potentially become dislodged or malpositioned
• Localization devices that do not require wires are increasing in popularity to overcome some of these issues:
  • For both techniques, the localization device, such as a radioactive seed, is implanted via mammographic or sonographic guidance prior to surgery:
    • Although initially used mostly for non-palpable breast lesions, use of these techniques is increasing in localization of lymph nodes, especially after neoadjuvant chemotherapy
• The use of neoadjuvant chemotherapy in node-positive breast cancer patients:
  • Can result in clinical downstaging of the axilla:
    • Allowing for de-escalation of axillary surgery with use of sentinel node biopsy rather than axillary dissection
  • Marking previously biopsied nodes and excision at time of breast surgery:
    • Has been shown to reduce false negative rates of sentinel node biopsy:
      • 6.8% vs. 19.8% without excision of clipped node
        • This is recommended by the National Comprehensive Cancer Network
• Radioactive seed placement has not been shown to interfere with the isotope utilized in sentinel node mapping

References

1. Lovrics PJ, Goldsmith CH, Hodgson N, et al. A multicentered, randomized, controlled trial comparing radioguided seed localization to standard wire localization for nonpalpable, invasive and in situ breast carcinomas. Ann Surg Oncol. 2011;18(12):3407-3414.

2. Cox CE, Russell S, Prowler V, et al. A prospective, single arm, multi-site, clinical evaluation of a nonradioactive surgical guidance technology for the location of nonpalpable breast lesions during excision. Ann Surg Oncol. 2016;23(1):3168-3174.

3. Caudle AS, Yang WT, Mittendorf EA et al. Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surg 2015;150(2):137-143.

4. Boughey JC, Ballman KV, Le-Petross HT et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance). Ann Surg. 2016;263(4):802-807.

5. Diego EJ, McAuliffe JF, Soran A, et al. Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes. Ann Surg Oncol. 2016;23(5):1549-1553.

• The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 trial was a randomized, double-blind, placebo-controlled trial of postoperative tamoxifen treatment (10 mg BID) for breast cancer patients with ER+ tumors and histologically negative lymph nodes.
  • Patient population:
    • 2644 patients with ER+ histologically node-negative breast cancers
  • Patients were administered the drug for at least 5 years
  • After 15 years of follow-up, compared with placebo:
    • Tamoxifen-treated patients were found to have benefited irrespective of age, menopausal status, or ER concentration for:
      • RFS:
        • 78% tamoxifen vs. 65% placebo
      • OS:
        • 71% tamoxifen vs. 65% placebo
    • A multivariate analysis indicated that all subgroups investigated showed benefit from tamoxifen treatment:
      • This included a reduction in rate of treatment failure at local and distant sites, a reduction in rate of incidence of new tumors in the contralateral breast, and a reduction in loco-regional recurrence after lumpectomy and breast irradiation
• While NSABP B-14 is known for establishing tamoxifen as an effective adjuvant therapy in ER+, node-negative patients:
  • Disease-free survival and OS were found to decrease over the 15-year follow-up in a subset of patients originally thought to have a favorable prognosis:
    • These findings prompted researchers to find a way to optimize treatment in this group:
      • Thus, the NSABP conducted the B-20 trial to evaluate the value of adding chemotherapy to tamoxifen for treatment regimens in ER+, node-negative patients:
        • Results from the B-20 trial after a 12-year follow-up demonstrated a significant improvement in disease-free survival with the addition of chemotherapy to tamoxifen when compared to tamoxifen alone

References

1. Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. A randomized trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor positive tumors. N Engl J Med.1989;320(8):479-484.

2. Fisher B, Jeong JH, Bryant, Anderson S, Dignam J, Fisher ER, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. Lancet. 2004;364(9437):858-868.

3. Newman LA, Mamounas EP. Review of breast cancer clinical trials conducted by the National Surgical Adjuvant Breast Project. Surg Clin N Am. 2007;87(2):279-305.

• To investigate the risk of ipsilateral breast events (IBEs):
  • In patients with DCIS treated with local excision without radiation:
    • The Eastern Cooperative Oncology Group (ECOG) and North Central Cancer Treatment Group:
      • Conducted a prospective trial between 1997 and 2002 known as the E5194 study:
        • Patients were stratified into two groups based on grade:
          • Low- and intermediate-grade DCIS measuring 2.5 cm or smaller, and high-grade DCIS measuring 1 cm or smaller
          • Margin widths of 3 mm or wider were required along with no residual calcifications on postoperative mammograms
        • The low- and intermediate-grade DCIS group:
          • Had a 12-year IBE rate of 14.4%
        • The high-grade group:
          • Had a 12-year IBE rate of 24.6% (p=0.003)
        • Larger tumor size was also found to be statistically significantly associated with developing an IBE (P = .01)
        • The risks of developing an IBE for either DCIS or invasive cancer:
          • Increased over time through 12 years of follow-up, without plateau
• Current literature reports a 50% decrease in local recurrence with radiotherapy after surgical excision of DCIS:
  • However, we continue to look for low risk subsets of patients with DCIS in whom the absolute benefit of radiation therapy of lumpectomy may be small
• The DCIS score (12-gene signature) was developed from tissue samples from the E5194 study:
  • With the goal of identifying low and high-risk subsets of patients with DCIS following lumpectomy alone
  • This assay utilized quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from tumor specimens from 327 patients with DCIS treated with surgical excision without radiation from the E5194 study:
    • The DCIS score of 0 to 100 (low less than 39, intermediate 39 to 54, high ≥ 55) was then designed to predict the recurrence of IBE overall, as well as DCIS or invasive cancer recurrence:
      • The DCIS score correlated with 10-year IBE risk of:
        • 10.6% in the low-risk group
        • 26.7% in the intermediate-risk group
        • 25.9% in the high-risk group
      • Young age and larger tumor size:
        • Also were found to be independent predictors of recurrence:
          • So, this test may be most beneficial in postmenopausal women with small tumors

References

1. Solin LJ, Gray R, Hughes LL, Wood WC, Lowen MA, Badve SS, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 Study. J Clin Oncol. 2015;33(33):3938-3944.

2. Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, et al. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013;105(10):701-710.

• The basic principles of reconstruction of cutaneous defects on the nose:
  • Require a thorough understanding of the anatomy of the nasal aesthetic subunits:
    • To facilitate appropriate excision and reconstruction
• The cutaneous surface of the nose:
  • Is divided into several aesthetic subunits, shown in Figure:
    • The most cephalad part of the nose:
      • Also called the root of the nose:
        • Encompasses a subunit extending from the medial aspect of the eyebrow from one side to the other
    • The middle third of the nose is divided into:
      • The dorsum and lateral walls
    • The lower third of the nose is divided into:
      • The tip of the nose, the alar subunit, and the columella
• Excision of any lesion involving any part of the cutaneous surface of the nose:
  • Therefore should include consideration of these subunits:
    • In planning not only the excision but also repair or reconstruction:
      • If the nasal aesthetic subunits are not considered in treatment planning:
        • The aesthetic result is not optimal