By Monica Smith

Chicago—Long-time attendees of the annual meeting of the American Society of Breast Surgeons (ASBS) have been enjoying Dr. Helen Pass’s talk on top breast papers, with yearly updates, for a decade. Fans appreciate Dr. Pass’s annual contribution as a labor of love; this year, her PubMed search yielded more than 18,000 English-language, clinical breast papers.

Because it’s impossible for her to include every innovative and outstanding article she finds, Dr. Pass limits her selections to those that stand out for one reason or another: “[whether] patients ask about them, or they’re subjects we argue over in tumor board, or they have the potential to be practice-changing,” said Dr. Pass, director, Division of Breast Surgery, and co-director, Women’s Breast Center, Stamford Hospital, Stamford, Conn.

1.van Schoor G, Otten J, den Heeten G, et al. Breast cancer among women over 75 years: An important public health problem. Eur J Public Health 2012;22:424-429.

The U.S. Preventive Services Task Force has not yet defined an upper age limit for mammography screening. Seeking to determine if breast cancer in elderly women is a public health concern, researchers analyzed data from the Netherlands where women over 75 are not prohibited from being screened, but are not sent a reminder letter.

They included 15,508 women who had been involved in a regimented screening program until age 75, but not after. All-cause median survival was 10 years, and more than 25% lived up to 15 more years. Only 341 were diagnosed with breast cancer, an incidence equivalent to that seen in screening mammography trials.

Of those who had breast cancer, 223 died, 73 from breast cancer, for a mortality risk of 30%. The researchers concluded that breast cancer in women over 75 is still a significant clinical concern.

Dr. Pass: “This is where we have to use some clinical judgment. A healthy elderly woman should be able to choose to get mammograms. You have to understand the patient’s goals. Most of the time, this is maintaining their independence and quality of life. My bias is that when you find cancer early, patients can be treated with less invasive measures, so I use this to justify continued screening to my internal medicine colleagues in patients without significant comorbidities.”

2.Sajid M, Hutson K, Akhter N, et al. An updated meta-analysis on the effectiveness of preoperative prophylactic antibiotics in patients undergoing breast surgical procedures. Breast J 2012;18:312-317.

Do patients need preoperative antibiotics for what is supposed to be a clean case? It’s a common argument. This paper was an analysis of nine randomized trials of the risk for subsequent infection in patients who did or did not have preoperative antibiotics. It included 3,720 patients evenly randomized to receive or not receive antibiotics.

The researchers found a significantly decreased risk for surgical site infection (SSI) in breast surgery patients who got preoperative antibiotics (P=0.0005), and the use of antibiotics was not associated with an increase in adverse reactions. They concluded antibiotics may be administered, but are not mandatory.

The ASBS’s position statement on the use of preoperative antibiotics states IV antibiotics are indicated for mastectomies or partial mastectomies with or without an axillary procedure, and with or without reconstruction; suggested for excisional open biopsies; and oral antibiotics should be considered if an accelerated partial breast irradiation (known as APBI) device is placed, and the antibiotic of choice is first-generation cephalosporin.

Dr. Pass: “It’s nice to have this data to guide management decisions.”

3.Lee M, Plews R, Rawal B, et al. Factors affecting lymph node yield in patients undergoing axillary node dissection for primary breast cancer: A single-institution review. Ann Surg Oncol 2012;19:1818-1824.

A total of 10 nodes has always been the hallmark of a complete axillary lymph node dissection (cALND). But surgeons sometimes find that despite performing a formal level I-II procedure, they get far fewer nodes in patients who had neoadjuvant chemotherapy.

This review, done at an institution of the National Comprehensive Cancer Network (NCCN), sought to determine if neoadjuvant chemotherapy reduces total lymph node yield. The researchers compared lymph node yield between 240 patients who received adjuvant chemotherapy and 903 patients who received primary surgical therapy alone.

The median lymph node yield was about the same in the adjuvant chemotherapy and primary surgery groups (15 and 17, respectively), but the range (1-46 and 2-64) was quite variable (P=0.0003). The neoadjuvant chemotherapy group had significantly more patients with fewer than 10 nodes.

The researchers suggested considering a revision of the NCCN guidelines regarding the number of lymph nodes for patients who have received neoadjuvant treatment.

Dr. Pass: “When it comes to the tumor board and the medical and radiation oncologist’s assessment of the completeness of your surgical technique, it’s nice to have this paper to support your contention that ‘I did do a formal operation; it’s just the biology of the disease.’”

4.Fitzal F, Mittlboeck M, Steger G, et al. Neoadjuvant chemotherapy increases the rate of breast conservation in lobular-type breast cancer patients. Ann Surg Oncol 2012;19:519-526.

Patients with invasive lobular carcinoma (ILC) tend not to respond as well to neoadjuvant chemotherapy as do patients with invasive ductal carcinoma (IDC) in terms of pathologic complete response. But that does not necessarily mean they do not benefit.

This study sought to establish the rate of conversion to breast-conserving therapy in patients previously considered not eligible. The researchers reviewed data on 325 patients, 21% of whom had ILC, participating in three neoadjuvant therapy trials.

They found a conversion rate to breast-conserving therapy of 45% in ILC patients and 52% in IDC patients. The local recurrence rate in ILC patients was the same whether they had breast-conserving therapy or mastectomy. They concluded that ILC patients should not be excluded from neoadjuvant chemotherapy.

Dr. Pass: “If we can convert 45% of women to [breast-conserving therapy] and that’s what they want, we should be willing to do it, especially since we’re not sacrificing oncologic outcomes. The other thing we have to remember is that patients with ILC who are ER/PR [estrogen receptor/progesterone receptor]-positive respond very well to neoadjuvant endocrine therapy. This is where multidisciplinary decision-making becomes very critical.”

5.Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor–positive breast cancer: ATLAS, a randomized trial. Lancet 2013;381:805-816.

The ATLAS trial, which investigated the effect of prolonging tamoxifen therapy, found recurrence, breast cancer mortality and overall mortality were all lower in patients randomized to an additional five years of tamoxifen after completing the initial five years. Non–breast cancer–related mortality, however, was about the same in both groups.

Although the risk for pulmonary embolism did go up in the 10-year group, mortality was the same. The risk for stroke was not significant; ischemic heart disease was lower in the longer-treated group. The risk for endometrial cancer was higher in the 10-year group, but the risk for dying from the disease still was far lower than the risk for dying from breast cancer.

Dr. Pass: “I think we all accept that 10 years of treatment is superior, but we worry about the side effects. However, for premenopausal women, 10 years of tamoxifen should be employed. They can’t get aromatase inhibitors, and they have a very low risk of uterine cancer.”

6.Weigert J, Steenbergen S. The Connecticut experiment: The role of ultrasound in the screening of women with dense breasts. Breast J 2012;18:517-522, 2012.

To assess the utility of ultrasound in women with dense breasts and a normal screening mammogram, researchers conducted a retrospective chart review of six radiology practices in Connecticut, which has a robust screening ultrasound program.

Of the 8,647 women who underwent screening ultrasound, about 5% met the indication for biopsy, and of those patients, 28% had cancer. There was one false-negative screening ultrasound. In this patient population, screening ultrasound had a positive predictive value of 6.7%, a negative predictive value of 99.9%, a sensitivity of 97% and a specificity of 95%.

There are some obstacles to adoption of the modality: in particular, the unwillingness of radiologists to embrace whole breast ultrasound, and the lack of a billing code for the screening ultrasound.

Dr. Pass: “But it will find cancers, and in women with dense breasts who have a [positive] family history, it’s definitely one more tool in the armamentarium that should be considered.”

7.Peled A, Foster R, Stover A, et al. Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts. Ann Surg Oncol 2012;19:3402-3409.

Researchers looked at postoperative complications, tumor involvement in the nipple areolar complex (NAC) and recurrence in 428 patients who underwent 657 total skin-sparing mastectomies over a nine-year period.

They found a partial nipple loss of 2%, a complete nipple loss of 1.5%, and skin flap necrosis in 11.9%. Only 3% of the patients had tumor involvement in the NAC, which was managed by repeat excision or radiation. Median local recurrence was 2% at 28 months, and 2.4% at three years. There was no recurrence in the nipple skin itself. They concluded that total skin-sparing mastectomy is oncologically safe with a low level of complications.

Dr. Pass: “They also made some technical suggestions. For example, ‘the extent of the periareolar incision must be limited to less than one-third of the diameter of the NAC or avoid the NAC entirely.’ Also, avoid tension on the skin for patients undergoing implant expansion.”

8.Setton J, Cody H, Tan L, et al. Radiation field design and regional control in sentinel lymph node-positive breast cancer patients with omission of axillary dissection. Cancer 2012;118:1994-2003.

Complete ALND is no longer recommended for women with a low axillary burden, but the value of additional axillary radiation is unknown. This paper assessed the impact of radiation field design on 326 patients with positive sentinel nodes who underwent breast-conserving therapy without cALND, 93% of whom received radiation.

At four years, regional control was 99%, local control was 98%, disease-free survival was 95%, and overall survival (OS) was 91%. They concluded that whole breast irradiation was sufficient treatment after breast-conserving therapy for patients with low axillary burden.

Dr. Pass: “So, we do not need to extend the radiation field to include the axilla, no matter how much our radiation oncologist is tempted. The point is we’re trying to minimize side effects. Radiation carries a risk just like surgery, so let’s not substitute one complication for another.”

9.Allred D, Anderson S, Paik S, et al. Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: A study based on NSABP Protocol B-24. J Clin Oncol 2012;30:1268-1273.

The B-24 trial demonstrated a 37% relative risk reduction in local recurrence and contralateral breast cancer in patients with ductal carcinoma in situ (DCIS) who received tamoxifen. Receptor status, however, was not a component of patient enrollment.

In this study, researchers evaluated the influence of receptor status on response. Of the 732 patients in the original study population with DCIS, 76% were ER-positive. In those patients, tamoxifen significantly decreased the risk for breast cancer; no benefit was found in ER-negative DCIS patients. They concluded tamoxifen should be considered in patients with ER-positive DCIS.

Dr. Pass: “Some people figure the risk–benefit ratio does not favor the addition of tamoxifen in patients with DCIS. But there’s a reported greater than 40% reduction in subsequent breast cancer … [in ER-positive patients who receive tamoxifen], so I really think a balanced conversation is necessary.”

10.Chlebowski R, Col N. Postmenopausal women with DCIS post-mastectomy: A potential role for aromatase inhibitors. Breast J 2012;18:299-302.

Women with DCIS are at increased risk for subsequent breast cancer, but are not commonly given tamoxifen due to the perception of an unfavorable risk–benefit ratio. In this subset analysis of the MAP.3 primary breast cancer prevention trial, researchers evaluated outcomes in the patients who underwent mastectomy for DCIS and received exemestane.

At 35 months’ median follow-up, there was a 65% reduction in invasive breast cancer and a 53% reduction in in situ breast cancer in women who received exemestane compared with those who received placebo. There was no difference in skeletal events, cardiovascular events or quality of life.

Dr. Pass: “In postmenopausal women who have had a mastectomy where you have concerns about tamoxifen, it’s good to know you can justify using an [aromatase inhibitor]. However, currently tamoxifen is the only FDA-approved drug for use in patients with DCIS.”

11.Truin W, Voogd A, Vreugdenhil G, et al. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer. Ann Oncol 2012;23:2859-2865.

Recent studies have shown that women with receptor-positive ILC who receive neoadjuvant chemotherapy have lower pathologic complete response than those with IDC. These researchers evaluated the effect of adding neoadjuvant chemotherapy to hormonal therapy in ILC and IDC patients.

In 19,609 IDC patients, 10-year survival was 69% for those who received hormonal therapy alone and 74% for those who also received chemotherapy. In the 3,685 ILC patients, however, 10-year survival was about 67% with or without the addition of chemotherapy. The researchers concluded adjuvant chemotherapy does not confer additional benefit to postmenopausal women with ILC receiving endocrine therapy.

Dr. Pass: “This reinforces what we know, but we need to be careful applying population-based information to one person. That’s where molecular profiling is much more specific and appealing.”

12.Verna S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783-1791.

The EMILIA trial found trastuzumab emtansine (TDM-1) significantly prolonged progression-free survival and OS compared with lapatinib plus capecitabine in women with HER2-positive advanced breast cancer who had already been treated with trastuzumab and a taxane.

Dr. Pass: “This is a fascinating new way to approach cancer. We know when we see success in a previously treated group that there really has to be good efficacy.”

Also Mentioned

  1. Lindstrom L, Karlsson E, Wilking U, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012;30:2601-2608.
  2. Amir E, Miller N, Geddie W, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 2012;30:587-592.
  3. Niikura N, Liu J, Hayashi N, et al. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 2012;30:593-599.

These three papers all found a change in receptor status.

Dr. Pass: “Taken together, they tell us that metastatic lesions need to be biopsied not to document that they’re metastatic disease, but to get a new receptor profile to guide subsequent therapy.”

  1. Baselga J, Cortes J, Kim S, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-119.
  2. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-529.
  3. Mehta R, Barlow W, Albain K, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012;367:435-444.
  4. Hadji P, Kieback D, Tams J, et al. Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German Cohort of TEAM. Ann Oncol 2012;23:2566-2572.
  5. Fontein D, Houtsma D, Hille E, et al. Relationship between specific adverse events and efficacy of exemestane therapy in early postmenopausal breast cancer patients. Ann Oncol 2012;23:3091-3097.