Skip to content

Case Study Cancer Of Breast

A.B. is a 61‐year‐old woman with metastatic HER2‐positive breast cancer. She is a self-employed consultant and travels extensively in the United States and internationally to work with her diverse clients. She is divorced and has three adult married children. She is active, in good health, and has no comorbid conditions. A.B. was treated with adriamycin plus cyclophosphamide (AC) followed by paclitaxel plus trastuzumab in the adjuvant setting. Two years later, she recurred with symptomatic disease (pain) in the liver. First‐line metastatic therapy included paclitaxel protein‐bound plus trastuzumab with good response and stable disease for seven months. A.B.’s liver lesions have now increased in size and number, and there are new bilateral pulmonary lesions. Her liver enzymes are within normal limits. After discussion with her oncologist and nurse practitioner (NP), A.B. begins an oral regimen of lapatinib plus capecitabine:

  • Capecitabine 2,000 mg in two divided doses
  • Lapatinib 1,250 mg in a single daily dose

A.B. is instructed to take her oral therapies as follows.

  • Capecitabine two tablets (500 mg each) twice daily for 14 days followed by a 7‐day rest period
  • Lapatinib five tablets (250 mg each) once daily, taken continuously

The following additional instructions are given to A.B. (Genentech USA, Inc., 2010; GlaxoSmithKline, 2010):

  • Take capecitabine within 30 minutes after a meal, approximately 10–12 hours apart (breakfast and dinner).
  • Take lapatinib on an empty stomach (30 minutes before or one hour after eating). The nurse suggests that A.B. take lapatinib at bedtime because A.B. says she does not snack during the evening.

The nurse gives A.B. a supply of blank calendars to complete for each cycle.

Note. Xeloda® (capecitabine) is a registered trademark of Genentech. Tykerb® (lapatinib) is a registered trademark of GlaxoSmithKline.

The nurse introduces the topic of adherence, telling A.B. that adherence means taking the medications as prescribed with respect to dose, time, and dietary intake. Nonadherence might result in the medications not working as expected or might increase side effects (ONS, 2009).

While talking with A.B. about her new regimen, the nurse notes several issues that could affect A.B.’s adherence to her oral regimen:

  • Financial: A.B. is self‐employed and self‐insured. She self‐pays for her health insurance, which has a high deductible and limited pharmaceutical benefit. She has already met the deductible for the current year.
  • Fragmented schedule: A.B. travels extensively and often has to reschedule medical appointments to meet her work obligations.
  • Frequent travel: A.B. often travels to Europe and Asia. Changing time zones may affect the medication schedule.

A.B. understands the nurse’s instructions about how and when to take her medication. She is motivated and confident that she can make this oral regimen work for her. “I like being in charge of my care and know that I can adapt my work and travel schedule,” says A.B. After reviewing possible side effects and how to contact the clinic after hours, A.B. is given prescriptions for one cycle of each medication to fill at her local retail pharmacy. The nurse also gives A.B. a listing of organizations that can help her with the cost of co‐payments for her medications and offers to help her apply if A.B. finds she needs financial assistance.

Two days later, the nurse calls A.B. to confirm that she has filled her prescriptions and is taking both medications as prescribed. A.B. says she’s “doing fine” and is taking the medications and has had no side effects. The nurse plans to call A.B. weekly during the first two cycles to monitor her adherence and side effects. A.B. is scheduled to come to clinic during the last few days of the capecitabine rest week (every three weeks) for an examination and toxicity assessment by the NP. She will be given a new prescription for the following cycle at each visit.

A.B. does well with cycles 1 and 2. She reports that she has taken “every pill when I was supposed to.” Her computed tomography (CT) scan following cycle 2 shows a good response with a decrease in size and number of liver and pulmonary lesions. She has experienced minimal side effects, noting only mild diarrhea early in each cycle and a faint skin rash on her chin, forehead, and upper arms. Her hands and feet are slightly erythematous and dry, indicating grade 1 hand‐foot syndrome. None of these side effects are significant enough to warrant dose interruption or modification, but A.B. is advised to call promptly if any of these symptoms increase in severity.

Because she is doing well and will be leaving on an extensive international trip, A.B. is given prescriptions for two cycles of medication and a return appointment is made for six weeks.

A.B. reschedules her appointment for a few days past the original date. When she is asked about adherence to her regimen over the last two cycles, A.B. says she did not do very well. When she got to the capecitabine rest week (week 2 of 3) of the first cycle while she was traveling, she did not continue to take the lapatinib. She states “I just forgot. I was so busy and I wasn’t in my familiar surroundings where I put the medicine bottle on my kitchen counter to remind me. I forgot all about it until I went to start the next cycle. I didn’t know what to do, so I just started the next cycle but it was a couple of days late. For that cycle, I did remember to take the lapatinib every day, but I missed a few doses of capecitabine here and there. It was hard to remember what to take when due to the time differences, and I was eating dinner at midnight some nights.”

Although the nurse had given A.B. a diary and treatment calendar for each cycle, A.B. did not take the calendar with her on her trip. The nurse talks with A.B. about the importance of adhering to the regimen as prescribed, explaining that the results they expect with this regimen are based on clinical studies in which patients took the medicine exactly as prescribed. Taking the medicines on a different schedule, or not taking them at all, might decrease the efficacy of the medicines. Or, if medication is taken incorrectly, side effects might increase. The nurse reminds A.B. that the calendar might have reminded her to continue lapatinib and when to restart capecitabine.

A.B. and her nurse are very tech‐savvy. She and the nurse find a smartphone application that will send her a text message when she is due for a dose of capecitabine or lapatinib. Because A.B.’s smartphone can be programmed to retain her home time zone, the message will come at the correct time in order to maintain her baseline dosing times. A.B. will have to keep in mind the administration instructions for both medicines—capecitabine with food; lapatinib on an empty stomach.

The NP feels that A.B. should return in three weeks rather than six weeks to ensure that she has been able to adjust her schedule to maintain optimal adherence with both medications in her regimen. She is also concerned that going back on continuous lapatinib dosing might increase the risk of side effects. A prescription is given for one cycle. The nurse reminds A.B. that the primary responsibility for adherence to an oral cancer therapy regimen remains with the patient and stresses the importance of maintaining the prescribed schedule for taking her medications and for seeing the NP on time. She is also due for an evaluation CT scan before her next visit, and the nurse assists her in making the radiology and return clinic appointments.

The following visit takes place as scheduled. A.B. used the smartphone app to help her stay on track with her medication and used the calendar to remind her about the general dosing regimen. She had a slight increase in the skin rash, but it was not severe enough to warrant dose interruption. There was no change in her mild diarrhea, which she was managing with dietary changes. The CT scan showed further response to the regimen, and she and the NP decided she would continue. Mutually, A.B. and the nurse agreed that she should plan to return to clinic every cycle until she was sure she could manage the dosing regimen without problems.

Key Points

  1. Evaluate the patient’s lifestyle and motivation for barriers to adherence to an oral regimen.
  2. Stress the importance of adherence and how nonadherence may decrease efficacy or
    increase toxicity.
  3. Work with the patient to modify or resolve lifestyle issues that interfere with adherence.
  4. Provide tools (calendar, diary, technology) to increase adherence.
  5. Prescribe only one cycle at a time until the patient has a proven adherence and toxicity track record.

General Adherence Resources

Patient Assistance Resources

Breast Cancer in the Very Young Patient: A Multidisciplinary Case Presentation

  1. David Mintzer,
  2. John Glassburn,
  3. Bernard A. Mason and
  4. Dahlia Sataloff
  1. Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA
  1. David Mintzer, M.D., Joan Karnell Cancer Center, 230 West Washington Square, Philadelphia, Pennsylvania 19106, USA. Telephone: 215-829-6088; Fax: 215-829-6104; e-mail: mintzerd{at}pahosp.com
  • Received June 19, 2002.
  • Accepted October 17, 2002.

Abstract

A case is presented that exemplifies many issues and controversies in the diagnosis and treatment of breast cancer in the very young. This woman was 22 years of age at diagnosis; she initially underwent breast-conservation therapy and adjuvant chemotherapy, retained fertility, had a subsequent uncomplicated pregnancy and delivery, and 7 years later developed a local recurrence in the breast. The discussion addresses risk factors, diagnosis, and treatment of breast cancer in the young; the impact of treatment on fertility; implications regarding pregnancy, and the management of local recurrence after breast conservation.

Previous SectionNext Section

Case Presentation

M.G. presented in 1993 at 22 years of age with a mass in her right breast. There was no family history of breast or ovarian cancer in a primary relative. Mammography demonstrated a 1.5-cm mass with associated microcalcifications. Ultrasound was negative. Excisional biopsy revealed a 2.2 × 1.8-cm infiltrating ductal carcinoma with an extensive intraductal component. Estrogen and progesterone receptors were negative, and margins were originally positive. She was offered breast-conservation therapy and ultimately underwent two re-excisions to achieve tumor-free margins. Sixteen axillary lymph nodes were negative for tumor. Postoperatively, she received methotrexate and 5-fluorouracil chemotherapy with concomitant radiotherapy of 50.40 Gy in 28 fractions to 17 × 16-cm parallel opposed tangential fields, with an additional 10 Gy electron boost to the tumor bed with 12 MeV electrons, for a total tumor dose of 60.40 Gy.

She remained free of recurrence for 7 years, with an uncomplicated pregnancy in 1999. However, routine mammography in 2000 showed new microcalcifications in the same quadrant as the prior lumpectomy. Biopsy revealed ductal carcinoma in situ with multiple areas of microinvasion. She subsequently underwent skin-sparing mastectomy with immediate transrectus abdominus myocutaneous flap reconstruction and presently remains free of recurrence.

Previous SectionNext Section

Features of Breast Cancer in Young Women:Dr. Dahlia Sataloff

Breast cancer is quite rare in very young women. It is a disease primarily of older women, with 75% of cases occurring in women over 50 years of age. Only 6.5% of cases occur in women under 40 years of age, and a mere 0.6% of cases in women under 30 years of age. Thus, in the U.S., only about 1,200 cases of breast cancer occur in women under 30 years of age each year (Fig. 1⇓) [1].

Figure 1.

Cumulative distribution of breast cancer diagnoses by age.Reproduced with permission [1].

Breast cancer may be more difficult to diagnose in young women. Breasts of younger women tend to be more nodular and are subject to fluctuation from the menstrual cycle. Lumps due to fibrocystic change are far more common in this age group, leading the clinician to have a lower index of suspicion for malignancy. In a study of 30 young women with breast cancer, the clinical examination was correctly deemed to be malignant in only 37% of patients [2]. Another 20% of findings were indeterminate. Almost half of the patients were thought to have benign disease and 30% were clinically consistent with a fibroadenoma. Cancer in young women can present as a circumscribed mass, and because fibroadenomas are common in this age group, this diagnostic error is understandable. However, this reinforces the need for tissue diagnosis on all breast masses in young women. The ability to diagnose breast cancer in older women is somewhat easier. The accuracy of physical examination in this group of patients is higher, reaching as high as 85% [2].

The accuracy of mammography is also lower in younger than in older women, whose breasts tend to be less dense. In the younger age group, one study showed only 55% of mammograms in women with cancer demonstrated clearly malignant findings, with another 22% indeterminate, raising the total suspicion of malignancy to 77% [2]. Twenty-three percent of mammograms in these women were read as clearly benign. Ultrasound showed malignant features in only 58% and was inconclusive in another 12%. Ultrasound was read as clearly benign in 30%, with 6 of 26 cases read as a fibroadenoma. Fine needle aspiration cytology has the greatest accuracy, with 78% definitely malignant and another 15% suspicious, raising the overall proportion to 93%.

When the results of physical examination, radiographic imaging, and fine needle aspiration cytology are combined, the classic triple test in diagnosis of breast disease, 95% of all cancers were recognized preoperatively [2]. Even though this is a high proportion, it is slightly lower than the quoted rate of 99%-100% for the triple test in the general population [3]. Other studies, however, have shown equivalent accuracy in the modified triple test in the diagnosis of palpable breast lesions in young women (modification refers to the use of ultrasound as opposed to mammography as the imaging component) [4].

Breast cancer in young women differs in several other respects. In a recent study, women with breast cancer presenting before age 36 were compared with cases obtained from the tumor registry at Mt. Sinai Medical Center from 1989 to 1997 [5]. There were slightly more than 100 patients under 36 years of age and roughly 600 patients 36 years of age or older. Younger women were more likely to have a positive family history. Eighty-seven percent of cancer in young women presented with a palpable mass, usually found by the patient herself. Since screening mammography is not recommended in young women, it is unusual for cancers in this group to be detected in this fashion. When a diagnostic mammogram was done, however, it was frequently positive.

The consequence of presenting more often with palpable disease rather than with a mammographic abnormality is that patients under age 36 frequently have larger, more advanced tumors. The median tumor size is 2 cm in young women compared with 1.5 cm in older women. Ductal carcinoma in situ is seen less frequently. The majority of younger women are diagnosed with stage II and III disease compared with stage 0 and I disease in women over age 36. More young patients with breast cancer are node positive; margins are involved more often and women are more likely to have an extensive intraductal component. In addition to being larger and having more positive margins, tumors in younger women tend to be more aggressive. Cancers are more poorly differentiated, more likely to be receptor negative, and more often aneuploid with a high S phase percentage [5].

In conclusion, physical examination and imaging studies are less accurate in younger women than in older women, underscoring the importance of maintaining a high index of suspicion for malignancy and obtaining a tissue diagnosis on all palpable lumps. Breast cancer in younger women can be a more aggressive disease and present at a later stage. Thus, treatment options may be different in this group as compared with older women.

Previous SectionNext Section

Etiology of Breast Cancer:Dr. Bernard Mason

Why would breast cancer occur in such a young woman? Such a young age of onset might suggest an associated genetic syndrome. I will discuss general models of risk for breast cancer, genetic causes, developmental causes, and potential environmental causes. The standard risk factors for breast cancer include age, family history, early menarche, late menopause, nulliparity or late age of first live birth, estrogen use, and dietary factors such as alcohol and possibly dietary fat [6]. None of these would predict for breast cancer in our patient.

The Gail model is one of the standard models of risk for breast cancer [7]. Based on the risk factor data derived from the Breast Cancer Detection Demonstration Project of the 1970s, this model incorporates information about the patient’s age, reproductive history, breast biopsies, and occurrence of breast cancer in first-degree relatives on the maternal side of the family. The Gail model does not incorporate information about other cancers such as ovarian cancer, second-degree relatives with cancer, or a paternal family history. Therefore, it does underestimate breast cancer risk in women from families with a gene mutation. Nonetheless, the Gail model has been validated with data from the Breast Cancer Prevention Study, predicting 155 cases of breast cancer in the placebo group during the follow-up period. In fact, there were actually 159 cases in over 6,000 women on that arm of the study, which makes the Gail model a fairly reliable predictor of breast cancer risk in a large population.

The Claus model [8], derived from data from the Cancer and Steroid Hormone Study, is based solely on family history of breast cancer. It includes both paternal and maternal family history of breast cancer as well as the ages of the affected individuals. However, other types of cancer are not taken into account in the Claus models. Therefore, this model, like the Gail model, may also significantly underestimate the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Neither of these models of breast cancer risk would predict for breast cancer in our young patient.

How much breast cancer is inherited? Approximately 5%-10% of breast cancers are attributable to germline mutations such as BRCA1 or BRCA2 [9–11]. Another 15%-20% of breast cancers are related to gene polymorphisms and environmental factors (so-called family clusters), and the rest of cases are sporadic and not related to genetic predisposition.

The BRCA1 and the BRCA2 gene mutations account for most known hereditary breast cancers. Features that indicate an increased likelihood of having a BRCA mutation include multiple cases of early-onset breast cancer, ovarian cancer with family history of breast or ovarian cancer, breast cancer and ovarian cancer in the same woman, bilateral breast cancer, Ashkenazi Jewish heritage, and male breast cancer.

The Li-Fraumeni syndrome is rare and is caused by germline mutations in the p53 gene on chromosome 17 [12]. Affected patients have a 50% risk of cancer by age 35, with a lifetime risk of cancer in about 90% of the women and 70% of the men. This disparity is due to the high frequency of breast cancer in women with p53 mutations. Other cancers include sarcoma, brain tumors, adrenocortical cancers, leukemia, and early-onset cancers of other types.

Cowden syndrome is a rare syndrome caused by a mutation in the PTEN gene on chromosome 10 [13, 14]. Affected patients have breast cancer or thyroid cancer at a young age, or uterine cancer; they are also often afflicted with multiple hamartomas.

Developmental factors may play a role in causing breast cancer in young women. In a recent study [15], the prevalence of breast cancer in young women was associated with very high birth weight (of the patient) or very high maternal age (of the patient’s mother), but not preterm birth. There was J-shaped association between birth weight and breast cancer risk, and also between maternal age and breast cancer, with a positive linear association for maternal age greater than 35 years versus 20-24 years.

Finally, environmental exposures after birth may increase the risk of breast cancer in young women. Hodgkin’s disease survivors, particularly those afflicted during teenage years, have an increased risk of breast cancer, with the ratio of observed to expected breast cancers as high as 75-fold [16]. This high risk of breast cancer seems to be related to radiation therapy. Other exposures to ionizing radiation, such as from fluoroscopy or nuclear weapon fallout, have been shown to increase the risk of breast cancer as well [17, 18].

Previous SectionNext Section

Breast Conservation Therapy in the Young Breast Cancer Patient:Dr. John Glassburn

Radiation therapy following local excision of breast cancer has been an accepted alternative to mastectomy for more than 40 years. However, not all patients are candidates for breast preservation, and over the years, the contraindications have become better defined [19]. Absolute contraindications include: A) pregnancy during the first or second trimester (radiation can be postponed until after delivery if the patient is in the third trimester); B) diffuse, indeterminate, or malignant microcalcifications; C) two or more tumors in separate breast quadrants; D) prior therapeutic radiation to the involved breast, and E) persistent positive margins following surgery. Relative contraindications include: A) large breast size; B) high tumor/breast ratios, and C) history of collagen-vascular disease, all of which may affect cosmesis.

Age is clearly a factor in local recurrence with younger patients having higher failure rates after limited surgery and radiation, as well as after mastectomy (Table 1⇓) [5, 20–27]. It is well documented that younger patients are more likely to have larger tumors and a greater likelihood of nodal involvement. They are also more likely to have higher grade tumors and more lymphovascular space involvement [5]. All of these factors may impact on the locoregional and distant failure rate.

It has also been demonstrated that the younger patient is more likely to have histologically an extensive intraductal component, defined as 25% or more of the primary tumor and intraductal carcinoma adjacent to the invasive border [22, 25]. This is felt by some to indicate a greater risk of residual intraductal cancer in the remaining breast. Holland et al. [24] demonstrated residual cancer 2 cm or more beyond the index lesion in 59% of patients with an extensive intraductal component.

Radiation dose and the use of chemotherapy also impact on local control. A recent report of a European Organization for Research and Treatment of Cancer trial of 5,318 patients demonstrated a reduction in local recurrences from 6.8% to 4.3% with a 16 Gy boost [20]. Chemotherapy also improves local control, with one study reporting a decrease in in-breast failures from 17% to 5% in young women [23].

In summary, young women have a higher failure rate both with mastectomy and breast conservation. The young patient should receive adequate counseling so that she can make an informed choice regarding treatment.

Table 1.

Effects of age on local failure

Previous SectionNext Section

Issues of Fertility and Pregnancy After Breast Cancer Treatment:Dr. David Mintzer

The diagnosis and treatment of breast cancer in younger women have implications regarding the possibility and safety of subsequent pregnancy. About 25% of women with breast cancer are premenopausal and may be desirous of childbearing following diagnosis and treatment, as exemplified in our patient who had her first child without complications 7 years after treatment that included chemotherapy. Over the past several decades, many women have decided to delay childbearing until later years. Since the diagnosis of breast cancer increases with age, more women may be in a situation where they have been diagnosed with breast cancer but not yet fulfilled their desires for having children. The questions that we must answer for them include: Following treatment for breast cancer, will it be possible to become pregnant? Will it be safe, both for myself and for my child? If it is deemed possible and safe, is there a time interval I should wait following treatment before trying to conceive? In this discussion, we will not address the treatment of breast cancer in women diagnosed during pregnancy.

While surgery and radiation therapy for breast cancer do not impair fertility, chemotherapy may. Amenorrhea is a common complication of chemotherapy (Table 2⇓) [37–40]. In addition to impairing fertility, premature menopause induced by chemotherapy has other potential negative health consequences, including premature osteopenia, atherosclerosis, vasomotor and genitourinary effects, and psychological effects [40]. As we offer chemotherapy to patients with lower and lower risks of recurrence, where the absolute magnitude of benefit becomes smaller, this benefit is potentially increasingly offset by the risk of these complications.

On the other hand, chemotherapy-induced amenorrhea may impact positively on the course of breast cancer, as this type of chemical castration in some (but not all) analyses is associated with an improved prognosis (as compared with patients who receive chemotherapy and do not become amenorrheic) [44–46]. However, this is controversial, may only apply to hormone receptor-positive patients, and may be further complicated by the now more routine use of tamoxifen in premenopausal patients.

The frequency of chemotherapy-induced amenorrhea relates to a number of factors, including type of chemotherapy (with alkylating agents, principally cyclophosphamide, being the main agents implicated), the total duration and dose of drug given, the age of the patient at time of treatment, and the concomitant use of hormonal therapy [37–39]. Because of a strong desire to avoid drugs that might impact on fertility, the patient presented here received only methotrexate and 5-fluorouracil (5-FU), which at the time she was treated in 1993 was a reasonable standard for node-negative patients, although subsequently proven to be inferior to cyclophosphamide, methotrexate, and 5-FU [47]. In general, patients older than 40 years who are treated with chemotherapy are likely to become amenorrheic, while patients under 40 years are more likely to continue to menstruate. However, this is a continuous variable, with the very youngest patients most likely to remain fertile (Fig. 2⇓).

Figure 2.

Probability of menopause during the first year after diagnosis.Reproduced with permission [39].

The concern that pregnancy subsequent to breast cancer diagnosis will increase the risk or rate of recurrence has been addressed in several series. The fear has been that elevated hormonal levels associated with pregnancy could stimulate regrowth of hormonally sensitive residual cancer cells that would have otherwise remained dormant. There is really no evidence to suggest this is true. Retrospective series have not suggested an increased rate of recurrence or death in patients who become pregnant [48–51]. However, there is concern that patients who become pregnant are selected. Therefore, authors have used case-controlled series matching pregnant patients with controls, stage for stage and for time from diagnosis. But again, no definite evidence exists that risk is increased.

We are sometimes asked to advise patients how soon it is “safe” to proceed with attempts to conceive. Clearly, at no point does the risk of recurrence vanish, but it does diminish with time. While some physicians might advise waiting at least 2-3 years after treatment for breast cancer, giving time for the majority of the more aggressive recurrences to manifest, the decision is very much a personal one. The patient and prospective father must balance the risk of recurrence along with other issues and desires, including the patient’s age, how long they are willing to wait, and their willingness to proceed with childbearing in the face of the risk of recurrence.

Of infants born to women who have been treated for breast cancer with chemotherapy, there are no data to suggest any increased risk of complications associated with pregnancy or of congenital malformations [37].

There are many changes occurring in the areas of breast cancer treatment and fertility, making it difficult to come to firm conclusions and recommendations. First, the overall database regarding amenorrhea, fertility, and pregnancy is small and not well defined. At the same time, many more women are being offered chemotherapy than in the past, as the treatment of node-negative women with chemotherapy is increasing. The fact that women delay childbirth until a later age raises the issues of breast cancer and fertility with increasing frequency. Further, the type of chemotherapy drugs utilized and the duration of treatment have changed. Most of the data come from patients who received long (6-12 month) courses of CMF (cyclophosphamide, methotrexate, 5-FU), whereas many women today receive only four doses of cyclophosphamide, usually with doxorubicin, and sometimes followed by a taxane. In addition, more premenopausal women are now treated with tamoxifen as well, since data suggest benefit with the addition of tamoxifen to chemotherapy in these hormone receptor-positive patients. Finally, advances in the knowledge and techniques in fertility, such as the harvesting of eggs, freezing fertilized embryos, or perhaps freezing unfertilized eggs or ovarian tissue, may allow pregnancies more frequently than in the past.

Table 2.

Incidence of amenorrhea according to patient age

Previous SectionNext Section

Recurrence After Breast Conservation Therapy:Dr. Dahlia Sataloff

Local recurrence is defined as the recurrence of cancer in a breast previously treated with breast-conservation therapy. These recurrences can either be a true recurrence or a second primary. Generally, tumors that recur in the same quadrant and of the same histology as the original tumor are considered a true recurrence, especially if the recurrence occurs relatively soon after original treatment. Late recurrences, recurrences in a different quadrant or those of different histology, are considered new primaries.

Recurrences usually occur in the same quadrant as the original tumor. Roughly 30%-50% of recurrences are detected by mammography alone [52–57]. The physical and radiographic findings of recurrence are the same as in the initial diagnosis of cancer. Of patients with local recurrence, roughly 5%-8% will have concurrent distant metastases and a slightly smaller percentage will have locally unresectable disease, leaving approximately 90% amenable to further surgery [30, 58, 59]. Factors predictive of local recurrence include issues reflecting the inherent aggressiveness of the original tumor such as tumor grade, lymphovascular invasion, and patient age. Other factors reflect the extensiveness of local disease such as inadequate or indeterminate margins and the presence of an extensive intraductal component.

Surgical treatment for local recurrence has generally been mastectomy. Reirradiation is generally not recommended. There is little published data on re-excision alone in this setting, but patients treated in this manner have a high risk of subsequent local relapse [60]. Therefore, re-excision should be reserved for patients who refuse mastectomy.

Reconstruction following radiation is best accomplished by myocutaneous flap, which can be done with skin-sparing techniques of mastectomy. Skin-sparing mastectomy preserves the maximum amount of skin by removing only the nipple areolar complex and the tumor biopsy scar and preserving the inframammary fold. This technique, first described in 1991, allows for superior cosmetic result without compromising the oncologic outcome [61]. The reported rate of skin recurrence following skin-sparing mastectomy is the same as for more traditional mastectomy, reflecting the fact that skin recurrence is related to the biology of the original tumor rather than caused by residual breast tissue left behind. Following radiation therapy, skin-sparing mastectomy can be accomplished but the skin flaps must be handled with particular care, as vascularity may have been compromised by prior therapy.

Previous SectionNext Section

Conclusion

Fortunately, our patient is doing well. But her course illustrates many of the issues that are somewhat specific to the diagnosis and treatment of breast cancer in the very young patient. As reviewed above, the diagnosis may be somewhat more difficult and delayed. Tumors tend to present at a slightly more advanced stage, and the biology of these tumors may be on average more aggressive. Breast-conservation therapy, while still an option for most women, does appear to be associated with a greater risk of local recurrence in younger patients. Fertility is commonly, but not always, preserved, depending in part on the age of the patient and the type and duration of chemotherapy utilized. Pregnancy subsequent to breast cancer diagnosis has not been demonstrated to be associated with identifiable risks to either the mother or the infant.

References

  1. Hankey BF, Miller B, Curtis R et al. Trends in breast cancer in younger women in contrast to older women. J Natl Cancer Inst Monogr1994;16:7–14.

  2. Ashley S, Royle GT, Corder A et al. Clinical radiological and cytological diagnosis of breast cancer in young women. Br J Surg1989;76:835–837.

  3. Vetto J, Pommier R, Schmidt W et al. Use of the “triple test” for palpable breast lesions yields high diagnostic accuracy and cost savings. Am J Surg1995;169:519–522.

  4. Vetto J, Pommier RF, Schmidt WA et al. Diagnosis of palpable breast lesions in younger women by the modified triple test is accurate and cost-effective. Arch Surg1996;131:967–972.

  5. Gajdos C, Tartter PI, Bleiweiss IJ et al. Stage 0 to stage iii breast cancer in young women. J Am Coll Surg2000;190:523–529.

  6. Colditz GA, Willett WC, Hunter DJ et al. Family history, age and risk of breast cancer. JAMA1993;270:338–343.

  7. Gail MH, Brinton LA, Byar DP et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst1989;81:1879–1886.

  8. Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer1994;73:643–651.

  9. Miki Y, Swensen J, Shattuck-Eidens D et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science1994;266:66–71.

  10. Wooster R, Bignell G, Lancaster J et al. Identification of the breast cancer susceptibility gene BRCA2. Nature1995;378:789–792.

  11. Couch FJ, DeShano ML, Blackwood MA et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med1997;336:1409–1415.

  12. Li FP, Fraumeni Jr JF. Soft tissue sarcomas, breast cancer, and other neoplasms: familial syndrome? Ann Intern Med1969;71:747–752.

  13. Eng C. Cowden syndrome. J Genet Counsel1997;6:181–192.

  14. Nelen MR, Padberg GW, Peeters EA et al. Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Genet1996;13:114–116.

  15. Innes K, Byers T, Schymura M. Birth characteristics and subsequent risk for breast cancer in very young women. Am J Epidemiol2000;152:1121–1128.

  16. Bhatia S, Robison LL, Oberlin O et al. Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med1996;334:745–751.

  17. Howe GR, McLaughlin J. Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer in the atomic bomb survivors study. Radiat Res1996;145:694–707.

  18. Little MP, Boice Jr JD. Comparison of breast cancer incidence in the Massachusetts tuberculosis fluoroscopy cohort and in the Japanese atomic bomb survivors. Radiat Res1999;151:218–224.

  19. Fowble B, Schultz D, Overmoyer B et al. The influence of young age on outcome in early stage breast cancer. Int J Radiat Oncol Biol Phys1994;30:23–33.

  20. Bartelink H, Collette L, Founquet A et al. Impact of a boost dose of 16 Gy on local control and cosmesis in patients with early breast cancer. The EORTC Boost vs. Not Boost Trial. Int J Radiat Oncol Biol Phys2000;48(suppl):111.

  21. Lichter A. Breast cancer. In: Leibel S, Phillips T eds. Textbook of Radiation Oncology. Philadelphia: WB Saunders, 1998;1013-1045.

  22. Elkhuizen PH, van de Vijver MJ, Hermans J et al. Local recurrence after breast conserving therapy for invasive breast cancer: high incidence of young patients and association with poor survival. Int J Radiat Oncol Biol Phys1998;40;859–867.

  23. Rose MA, Henderson IC, Gelman R et al. Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure. Int J Radiat Oncol Biol Phys1989;17:711–717.

  24. Holland R, Connolly JL, Gelman R et al. The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. J Clin Oncol1990;8:113–118.

  25. Haffty BG, Fischer D, Rose M et al. Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. J Clin Oncol1991;9:997–1003.

  26. Kurtz J, Jacquemier J, Amalric R et al. Why are local recurrences after breast-conserving therapy more frequent in younger patients? J Clin Oncol1990;8:591–598.

  27. Ryoo MC, Kagan AR, Wollin M et al. Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. Radiology1989:172:555–559.

  28. Boyages J, Recht A, Connolly J et al. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol1990;19:29–41.

  29. Clarke D, Le M, Sarrazin D et al. Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys1985;11:137–145.

  30. Delouche G, Bachelot F, Premont M et al. Conservation treatment of early breast cancer: long term results and complications. Int J Radiat Oncol Biol Phys1987;13:29–34.

  31. Fourquet A, Campana F, Zafrani B et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys1989;17:719–725.

  32. Fowble B, Schultz D, Overmoyer B et al. The influence of young age on outcome in early stage breast cancer. Int J Radiat Oncol Biol Phys1994;30:23–33.

  33. Haffty B, Fischer D, Rose M et al. Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. J Clin Oncol1991;9:997–1003.

  34. Kurtz J, Jacquemier J, Amalric R et al. Why are local recurrences after breast-conserving therapy more frequent in younger patients? J Clin Oncol1990;8:591–598.

  35. Matthews R, McNeese M, Montague E et al. Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy. Int J Radiat Oncol Biol Phys1988;14:659–663.

  36. Veronesi U, Salvadori B, Luini A et al. Conservative treatment of early breast cancer. Long-term results of 1232 cases treated with quadrantectomy, axillary dissection, and radiotherapy. Ann Surg1990;211:250–259.

  37. Reichman BS, Green KB. Breast cancer in young women: effect of chemotherapy on ovarian function, fertility and birth defects. J Natl Cancer Inst Monogr1994;16:125–129.

  38. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol1996;14:1718–1729.